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        <title>Frontiers in Immunology | New and Recent Articles</title>
        <link>https://www.frontiersin.org/journals/immunology</link>
        <description>RSS Feed for Frontiers in Immunology | New and Recent Articles</description>
        <language>en-us</language>
        <generator>Frontiers Feed Generator,version:1</generator>
        <pubDate>2026-05-13T09:37:13.692+00:00</pubDate>
        <ttl>60</ttl>
        <item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1808107</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1808107</link>
        <title><![CDATA[Metabolic reprogramming of cholesterol biosynthesis drives macrophage-mediated immune suppression in HPV-negative cervical adenocarcinoma]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Jianing Zhang</author><author>Wenjuan Wei</author><author>Yajun Zhang</author><author>Daqing Wang</author>
        <description><![CDATA[BackgroundCervical adenocarcinoma is an increasingly common and aggressive subtype of cervical cancer with marked biological heterogeneity. Accumulating evidence suggests that HPV-positive and HPV-negative adenocarcinomas exhibit distinct immune microenvironments, but the underlying mechanisms remain unclear.MethodsPublicly available single-cell RNA sequencing datasets of cervical adenocarcinoma and normal cervical tissues were systematically analyzed using integrated bioinformatic approaches, including cell clustering, copy number variation inference, metabolic pathway analysis, and cell–cell communication modeling. Key findings were validated through in vitro experiments using cervical cancer cell lines, macrophage polarization assays, metabolic measurements, ELISA, immunofluorescence, and CD8+ T cell functional analyses.ResultsSingle-cell analysis revealed profound differences in cellular composition and immune states between HPV-negative and HPV-positive adenocarcinomas. HPV-negative tumors exhibited increased immune infiltration but were enriched for exhausted CD8+ T cells and immunosuppressive SPP1+ macrophages. Malignant epithelial cells from HPV-negative adenocarcinoma displayed distinct metabolic reprogramming characterized by activation of cholesterol biosynthesis pathways, elevated DHCR7 expression, and accumulation of the oxysterol 27-hydroxycholesterol (27-HC). Functionally, 27-HC induced macrophage polarization toward an immunosuppressive phenotype and promoted SPP1 secretion. Macrophage-derived SPP1, in turn, enhanced DHCR7 expression and 27-HC production in tumor cells via CD44, forming a positive feedback loop that reinforced immune suppression. Disruption of DHCR7 attenuated macrophage-mediated immunosuppression and alleviated CD8+ T cell exhaustion.ConclusionsThis study identifies a DHCR7–27-HC–SPP1 metabolic–immune axis that drives immune escape in HPV-negative cervical adenocarcinoma, highlighting cholesterol metabolism as a potential therapeutic vulnerability.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1820785</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1820785</link>
        <title><![CDATA[Post-translational modifications in retinoblastoma: mechanisms, immune regulation, and therapeutic opportunities]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Lifei Xu</author><author>Bin Wang</author><author>Wenwei Li</author><author>Xiandan Luo</author><author>Lixia Wang</author><author>Yi Zheng</author>
        <description><![CDATA[Retinoblastoma is an early-childhood retinal malignancy driven predominantly by biallelic RB1 inactivation and consequent RB–E2F checkpoint deregulation. Post-translational modifications (PTMs) add a rapid, reversible regulatory layer that rewires RB-centered signaling, chromatin control, metabolic adaptation, and therapy resistance. This review summarizes PTM mechanisms relevant to retinoblastoma, highlighting phosphorylation- and ubiquitination-centric circuits, as well as acetylation and methylation that modulate RB pathway function and downstream oncogenic phenotypes. We discuss actionable therapeutic opportunities, including compounds and degraders targeting PTM enzymes, and emphasize underexplored modifications such as SUMOylation, lactylation, and glycosylation that warrant systematic investigation in retinoblastoma. Finally, we integrate PTM biology with emerging immunotherapies and propose rational PTM–immunotherapy combinations and biomarker-guided translation to improve durable eye salvage and metastatic control.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1846052</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1846052</link>
        <title><![CDATA[Divergent immune cascades activated by metabolic versus mechanical exercise intensity: revisiting cytokine heterogeneity in “moderate-intensity exercise”]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Jia-wen Wang</author><author>Jian-Jun Xun</author><author>Li-Na Jian</author>
        <description><![CDATA[“Moderate-intensity exercise” is widely regarded as anti-inflammatory; however, meta-analyses of key cytokines have yielded highly inconsistent results. We argue that this inconsistency reflects not mere statistical noise, but a fundamental conceptual conflation: aerobic exercise intensity is anchored to metabolic rate (%VO2max), whereas resistance training intensity is anchored to neuromuscular force output (%1RM). These quantify orthogonal dimensions of physiological stress and are not physiologically interchangeable, yet the shared label “moderate intensity” groups them into a single exposure category. Crucially, these two exercise modalities activate inflammatory signaling pathways in opposite directions: aerobic exercise engages a myokine-mediated anti-inflammatory axis (IL-6→AMPK→IL-10), whereas resistance exercise initiates a damage–repair immune cascade (DAMPs→M1→M2 macrophage polarization), yielding fundamentally divergent acute cytokine profiles. The aggregation of incommensurable physiological stimuli is a major contributor to the extreme heterogeneity reported in current meta-analyses. The proposed “dual-axis classification” quantifies metabolic and mechanical dimensions in parallel rather than as mutually exclusive categories; for mixed-modality interventions (e.g., HIIT), both dimensions should be reported concurrently. Accordingly, we recommend that future studies adopt a dual-axis framework that reports metabolic and mechanical loads separately, implement time-resolved inflammatory sampling, and apply causal inference methods to re-stratify existing evidence by exercise modality, thereby addressing this central source of inconsistency.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1868391</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1868391</link>
        <title><![CDATA[Editorial: Understanding eQTLs and their Association with Spondyloarthropathies]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Editorial</category>
        <author>Matteo Vecellio</author>
        <description></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1778171</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1778171</link>
        <title><![CDATA[Risk of intestinal involvement in mucocutaneous-onset Behçet’s disease: data from the AIDA network registry]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Brief Research Report</category>
        <author>Antonio Vitale</author><author>Valeria Caggiano</author><author>Jessica Sbalchiero</author><author>Francesco Gavioli</author><author>Giuseppe Lopalco</author><author>Gaafar Ragab</author><author>Silvana Guerriero</author><author>Ibrahim Almaglouth</author><author>Abdurrahman Tufan</author><author>Roberto Giacomelli</author><author>Haner Direskeneli</author><author>Piero Ruscitti</author><author>Gülen Hatemi</author><author>Francesco Carubbi</author><author>Ezgi Deniz Batu</author><author>Seza Ozen</author><author>Jurgen Sota</author><author>Henrique Ayres Mayrink Giardini</author><author>Micol Frassi</author><author>Petros P Sfikakis</author><author>Maria Morrone</author><author>Federica Gatti</author><author>Amina Maher</author><author>Ayman Abdel-Monem Ahmed Mahmoud</author><author>Rosanna Dammacco</author><author>Hamit Kucuk</author><author>Riza Can Kardas</author><author>Ibrahim Yahya Cakir</author><author>Letizia Pia di Corcia</author><author>Fatma Alibaz Öner</author><author>Gizem Sevik</author><author>Martina Gentile</author><author>Alican Karakoc</author><author>Alessia Alunno</author><author>Hulya Ercan Emreol</author><author>Francesca Crisafulli</author><author>Maria Tektonidou</author><author>Francesco Ciccia</author><author>Maissa Thabet</author><author>Serena Bugatti</author><author>Alessandra Milanesi</author><author>Maria Sole Chimenti</author><author>Benedetta Monosi</author><author>Matteo Piga</author><author>Alberto Floris</author><author>Andrea Hinojosa-Azaola</author><author>Guillermo Arturo Guaracha-Basañez</author><author>Cecilia Beatrice Chighizola</author><author>José Hernández-Rodríguez</author><author>Marco Cattalini</author><author>Marcello Govoni</author><author>Ombretta Viapiana</author><author>Adele Civino</author><author>Daniela Opris-Belinski</author><author>Carla Gaggiano</author><author>Rosaria Talarico</author><author>Annarita Giardina</author><author>Giacomo Emmi</author><author>Piercarlo Sarzi Puttini</author><author>Maria Cristina Maggio</author><author>Paola Parronchi</author><author>Piero Portincasa</author><author>Alejandra de-la-Torre</author><author>Juanita Cardona-López</author><author>Stefano Gentileschi</author><author>Angela Mauro</author><author>Gian Domenico Sebastiani</author><author>Maria Francesca Gicchino</author><author>Ali Şahin</author><author>Donato Rigante</author><author>Emre Bilgin</author><author>Emanuela Del Giudice</author><author>Luciana Breda</author><author>Amato De Paulis</author><author>Alberto Lo Gullo</author><author>Şükran Erten</author><author>Samar Tharwat</author><author>Lampros Fotis</author><author>Maier Armin</author><author>Antonella Insalaco</author><author>Anastasios Karamanakos</author><author>Alessandro Conforti</author><author>Özgül Soysal Gündüz</author><author>Abdelhfeez Moshrif</author><author>Francesca Li Gobbi</author><author>Stefania Costi</author><author>Elena Bartoloni</author><author>Patrizia Barone</author><author>Serena Guiducci</author><author>Andrés González-García</author><author>Inés Hernanz Rodriguez</author><author>Giovanni Conti</author><author>Annamaria Iagnocco</author><author>Fatos Önen</author><author>Sulaiman M. Al-Mayouf</author><author>Ali İbrahim Hatemi</author><author>Alberto Balistreri</author><author>Claudia Fabiani</author><author>Luca Cantarini</author>
        <description><![CDATA[ObjectiveBehçet’s disease (BD) may initially manifest solely with mucocutaneous involvement. This study aimed to identify demographic and clinical factors associated with subsequent intestinal involvement in patients presenting exclusively with mucocutaneous manifestations during early disease stages.MethodsData were obtained from the International AutoInflammatory Disease Alliance Network registry dedicated to BD; a Bayesian statistical approach was employed to address the limited sample size resulting from subgroup stratifications.ResultsIn total, 328 BD patients with exclusively mucocutaneous onset were enrolled; of these, 46 (14%) developed intestinal involvement over time. The risk of ocular involvement was higher among patients with intestinal manifestations (OR: 3.02, 95% CrI: 1.24–6.08; posterior probability: 99.3%). Minor aphthous ulcers without major aphthosis were protective towards intestinal involvement (OR: 0.47, 95% CrI: 0.22–0.98; posterior probability: 97.98%). Conversely, major aphthous ulcers increased the risk (OR: 3.25, 95% CrI: 1.50–7.02; posterior probability: 99.7%), along with the combination of oral major aphthosis with: i) genital aphthosis (OR = 2.77, 95%CrI: 1.14-6.58; posterior probability: 98.45%); ii) pseudofolliculitis (OR = 3.18, 95%CrI: 1.15-8.33; posterior probability: 98.72%); iii) genital aphthosis plus pseudofolliculitis (OR = 5.22, 95%CrI: 1.71-16.35; posterior probability of 99.77%). Pseudofolliculitis plus cutaneous manifestations other than erythema nodosum were protective against intestinal involvement (OR = 0.01, 95%CrI: 0.0-0.98; posterior probability: 97.55%).ConclusionMajor aphthosis was the strongest factor associated with intestinal involvement in BD patients initially presenting with mucocutaneous symptoms only. In such patients, intestinal involvement correlated with increased risk of ocular inflammation.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1817221</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1817221</link>
        <title><![CDATA[Serplulimab combined with gemcitabine, nab-paclitaxel, and stereotactic body radiotherapy versus gemcitabine and nab-paclitaxel as first-line treatment for recurrent or metastatic pancreatic ductal adenocarcinoma: a randomized, open-label, multicenter, phase III clinical trial (WGOG-PAN 006/ICSBR-2)]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Brief Research Report</category>
        <author>Xin Wang</author><author>Pei Zhang</author><author>Dan Cao</author><author>Huanji Xu</author>
        <description><![CDATA[BackgroundPancreatic ductal adenocarcinoma remains a malignancy with a dismal prognosis, characterized by a median overall survival of less than one year in the metastatic setting despite standard-of-care chemotherapy regimens like gemcitabine plus nab-paclitaxel. The PDAC tumor microenvironment is notoriously immunosuppressive, rendering single-agent immune checkpoint inhibitors largely ineffective. Stereotactic Body Radiotherapy has emerged as a potential strategy to induce immunogenic cell death and remodel the TME. Based on promising Phase II data demonstrating a 78.48% 6-month progression-free survival rate with the triplet combination of GnP, Serplulimab and SBRT, this Phase III trial aims to validate the efficacy of this “radio-immuno-chemotherapy” strategy.MethodsThis prospective, randomized, open-label, multicenter Phase III study will enroll 198 patients with recurrent or metastatic PDAC who are naive to systemic therapy for advanced disease. Participants will be randomized (1:1) to the Experimental Group receiving Serplulimab (300 mg IV, Q3W) combined with Gemcitabine 1000 mg/m² + nab-Paclitaxel 125 mg/m², Days 1, 8, Q3W and SBRT (33–50 Gy/5 fractions) initiated in Cycle 2, or the Control Group receiving GnP alone.OutcomesThe primary endpoint is Overall Survival. Secondary endpoints include progression-free survival, Objective Response Rate, Disease Control Rate, and safety profiles assessed via NCI-CTCAE v5.0. Exploratory endpoints include cyclic multiplex tissue staining assays to evaluate immune spatial interactions.DiscussionThis study addresses the critical unmet need in advanced PDAC by evaluating a mechanistic synergy between cytotoxic debulking, radiation-induced immune priming, and checkpoint blockade. If successful, this regimen could establish a new standard of care.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1779393</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1779393</link>
        <title><![CDATA[Complement activation in patients with post-acute sequelae after SARS-CoV-2 infection]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Brief Research Report</category>
        <author>Madlene Holmqvist</author><author>Dick J. Sjöström</author><author>Katherine Carlson</author><author>Birgitta Gullstrand</author><author>Anders A. Bengtsson</author><author>Robin Kahn</author><author>Tom E. Mollnes</author><author>Per Åkesson</author><author>Per H. Nilsson</author><author>Fredrik Kahn</author>
        <description><![CDATA[IntroductionPost-acute sequelae of SARS-CoV-2 (PASC) may develop after SARS-CoV-2 infection and cause a wide range of symptoms that can persist for years. Several pathophysiological mechanisms have been proposed, including dysregulation of the complement system.MethodsIn this study, we analysed markers of complement activation in a cohort of patients with PASC, up to 33 months after the initial infection. We measured the complement activation markers C3bc, C3bBbP and TCC in 38 PASC patients with an initial mild COVID-19 infection, 10 PASC patients with an initial severe COVID-19 infection and 80 control subjects who had recovered completely after a COVID-19 infection.ResultsAlthough the patients with an acute mild SARS-CoV-2 infection had a trend towards more severe PASC, we could not find any significant differences in complement activation markers between these patients and controls.ConclusionWe could not find convincing evidence of activation of the complement system in PASC patients.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1808989</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1808989</link>
        <title><![CDATA[Serum inflammatory cytokines in the progression of depression]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Qing Feng</author><author>Zhen Yuan</author><author>Qi An</author><author>Kang Wang</author><author>Xiaohui Liu</author>
        <description><![CDATA[Depression is increasingly recognized as a multifactorial disorder in which immune dysregulation contributes substantially to disease initiation, progression, and treatment response. Among the immune mediators implicated, serum inflammatory cytokines—including IL-1β, IL-6, TNF-α, IFN-γ, and C-reactive protein—have emerged as key links between peripheral inflammation and central nervous system dysfunction. These cytokines influence depression-related pathophysiology by activating innate immune signaling pathways, including TLR4, NF-κB, MAPK, and the NLRP3 inflammasome, while also reshaping tryptophan–kynurenine metabolism through IDO1 and TDO2. The resulting alterations impair monoaminergic neurotransmission, enhance glutamatergic excitotoxicity, suppress BDNF-dependent neuroplasticity, and promote microglia-mediated neuroinflammation. Clinical studies further associate inflammatory cytokine profiles with symptom severity, cognitive dysfunction, suicidality, and illness chronicity, supporting their potential value as biologically informative markers in depression. Emerging therapeutic evidence indicates that anti-inflammatory bioactive compounds, conventional antidepressants with immunomodulatory properties, and rapid-acting agents such as ketamine may partially exert their effects by normalizing cytokine-associated pathways. This review summarizes current mechanistic and clinical evidence linking serum inflammatory cytokines to depression and highlights their potential as therapeutic targets in precision psychiatry.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1826191</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1826191</link>
        <title><![CDATA[Neutrophil extracellular traps in gout: from immune defense to pathological dynamic equilibrium]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Fangfang Wang</author><author>Ning Tie</author><author>Yong Jin</author><author>Hongbin Li</author>
        <description><![CDATA[Gout is an aseptic inflammatory disease caused by monosodium urate (MSU) crystal deposition. Its clinical signs go beyond the intense pain of acute arthritis to include structural damage such as chronic synovitis, bone erosion, and tophus formation. The long-term progression and recurring episodes of inflammation pose significant challenges in managing the disease. While hyperuricemia creates the metabolic basis, only a small percentage of patients develop gout, indicating that activation of the innate immune system is essential for its development. Recently, neutrophil extracellular traps (NETs) have become recognized as key mediators connecting metabolic issues to inflammatory responses, representing an important breakthrough in understanding gout pathogenesis. Initially, NETs are considered a host defense mechanism that protects against microbial invasion, where neutrophils release a web-like structure made of chromatin fibers and granular proteins to trap and eliminate microbes. However, in gout, a non-infectious disease, NETs have roles that extend beyond their traditional function, acting as a “double-edged sword”: they help limit acute inflammation but can also contribute to tissue damage and disease progression during the chronic phase, with their function changing according to the microenvironment. This review systematically discusses the mechanisms of NETs in gout development and examines their potential in diagnosing and treating the disease.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1810955</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1810955</link>
        <title><![CDATA[Generation of functional canine TIL products for solid tumors]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Kay M. Foos</author><author>Veethika Pandey</author><author>Michael W. Jennings</author><author>Daniel J. Powell</author><author>Nicola J. Mason</author>
        <description><![CDATA[Immunotherapy based on the adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) has proven effective in treating human metastatic melanoma patients, but success in tumors with lower mutational burdens remains a challenge. Preclinical evaluation of cellular therapies commonly relies on murine models, which often require implantation of tumors into immunocompromised mice and thus do not accurately reflect the complex tumor-immune interactions seen in patients. Alternatively, spontaneous tumors in client-owned dogs serve as an underutilized and valuable parallel patient population for investigating the effectiveness of adoptive cell therapy in an immunocompetent host. However, TILs have been largely unexplored in dogs. Leveraging canine cancer patients with naturally occurring low tumor mutational burden (TMB) cancer types to study TIL therapy aims to enhance preclinical translatability. To evaluate the feasibility of TIL therapy in the veterinary sector, we developed protocols to reliably expand TILs from canine oral melanoma and appendicular osteosarcoma, despite low T cell frequencies in tumor digests. A subset of these TIL products showed reactivity to autologous tumor cells from fresh tumor digests as well as early passage cell lines. Lack of TIL reactivity in a beta-2-microglobulin (B2M)-ablated canine melanoma sample confirmed that recognition was major histocompatibility complex (MHC) class I-dependent. Together, these data establish the feasibility of generating functional canine TIL products and pave the way for comparative trials to evaluate TIL efficacy and novel strategies to enhance responses in low-TMB malignancies.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1789297</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1789297</link>
        <title><![CDATA[Peripheral nerve remodeling in the tumor microenvironment: neuro-immune crosstalk, molecular mechanisms, and precision therapeutic]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Huiying Liu</author><author>Xunjun Li</author><author>Jiang Yu</author><author>Tao Chen</author>
        <description><![CDATA[As a crucial component of the tumor microenvironment, the nervous system modulates tumor initiation, progression, and metastasis. Conversely, tumors actively hijack and reshape neural structures to activate nerve-dependent developmental and regenerative processes that promote their own growth and survival. Despite extensive progress in tumor-neural crosstalk, the molecular mechanisms underlying neuro-immune coordination in peripheral nerve remodeling remain incompletely understood, and integrated strategies targeting this axis to overcome immunotherapy resistance are still lacking. This review comprehensively examines the phenotypic and functional remodeling of the peripheral nervous system within the tumor microenvironment, with a focus on neuro-immune crosstalk between neural cells, immune cells and cancer cells. We systematically analyze phenotypic remodeling in neurons and glial cells, with particular emphasis on autonomic nerve differentiation, functional reprogramming of the neurotrophin family, and the regulatory roles of immune cells in these processes. Finally, we discuss precision therapeutic strategies including β-adrenergic blockades, neurotrophin signaling inhibition, surgical and pharmacological denervation, and combinatorial regimens with immunotherapy, highlighting their translational potential in cancer treatment.Neuro-immune crosstalk in the tumor microenvironment: schematic of four core interaction nodes: This schematic illustrates the bidirectional interactions between peripheral nerves and immune cells within the tumor microenvironment. Schwann cells engage in antigen presentation and cytokine signaling with tumor-associated macrophages and lymphocytes. Sympathetic-derived norepinephrine drives T cell exhaustion and myeloid-derived suppressor cell expansion, while parasympathetic-derived acetylcholine activates α7 nicotinic acetylcholine receptors on immune cells to suppress NF-κB signaling. Macrophage- and lymphocyte-derived NGF and BDNF establish positive feedforward loops that amplify tumor-neural-immune interactions. Together, these interconnected mechanisms support tumor innervation, progression and immune evasion, positioning the neuro-immune axis as an emerging therapeutic target for cancer treatment.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1795363</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1795363</link>
        <title><![CDATA[Hyperthermia enhances the efficacy of PD-1 inhibitor plus chemotherapy in PD-L1 CPS-negative advanced gastric cancer]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Weihang Li</author><author>Xin Sun</author><author>Ping Li</author><author>Ting Wang</author><author>Panling Xu</author>
        <description><![CDATA[BackgroundAdvanced gastric cancer with negative PD-L1 combined positive score (CPS) responds poorly to immunotherapy. This study investigated the efficacy of hyperthermia combined with a PD-1 inhibitor and chemotherapy in this patient population.MethodsIn this retrospective study, 72 patients with PD-L1 CPS-negative advanced gastric cancer were enrolled. 37 received hyperthermia plus PD-1 inhibitor and SOX chemotherapy, while 35 received PD-1 inhibitor and chemotherapy alone. Propensity score matching (PSM) was applied. Progression-free survival (PFS) was the primary endpoint. Adverse events and circulating tumor cell dynamics were also assessed.ResultsAfter PSM, baseline characteristics were well-balanced. The CIH group showed significantly prolonged PFS compared to the CI group, both before and after matching (P = 0.00037 and P = 0.0011, respectively). The CIH group also had a significantly lower incidence of fatigue and anorexia (P<0.05). Although circulating tumor cell (CTC) counts increased in both groups after treatment, the post-treatment count and the magnitude of increase were significantly greater in the CIH group (P<0.001), potentially indicating enhanced therapy-induced immune activation and tumor cell death.ConclusionThe addition of hyperthermia to PD-1 inhibitor and chemotherapy significantly improves PFS and reduces specific adverse events in patients with PD-L1 CPS-negative advanced GC. This distinct CTC dynamic change, although still requiring further verification, may offer a potential mechanistic insight into the significant efficacy of this combined strategy.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1801628</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1801628</link>
        <title><![CDATA[The role of the complement system in gastrointestinal-related diseases]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Bo Yong</author><author>Zixiang Luo</author><author>Bo Luo</author><author>Jinbo Liu</author><author>Zhangrui Zeng</author><author>Xiaoli Zheng</author>
        <description><![CDATA[The complement system bridges innate and adaptive immunity, orchestrating immune surveillance and maintaining tissue homeostasis. This review summarizes the role of the complement system in gastrointestinal-related diseases, including its function in innate immunity, impact on adaptive immunity, and regulatory role under physiological and pathological conditions in the gut. The activation pathways, regulatory mechanisms, and interactions of the complement system with the gut microbiome are crucial for maintaining intestinal homeostasis. Genetic deficiencies or excessive activation of the complement system are closely associated with the development of various intestinal diseases, including infections, inflammatory bowel disease (IBD), and tumors. This review also explores the role of the complement system in the tumor microenvironment (TME) of the gut and its potential as a therapeutic target. By deepening our understanding of the mechanisms by which the complement system operates in gastrointestinal diseases, we can provide a theoretical foundation for the development of novel treatment strategies.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1827181</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1827181</link>
        <title><![CDATA[Convergent death programs in chronic obstructive pulmonary disease: how pyroptotic and ferroptotic crosstalk reshapes therapeutic paradigms]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Aisi Huang</author><author>Shiming Liu</author><author>Jiao Lan</author>
        <description><![CDATA[Chronic obstructive pulmonary disease (COPD) remains a leading cause of global mortality, yet current therapies principally target bronchodilation and broad anti-inflammatory suppression rather than the regulated cell death programs driving tissue destruction. Pyroptosis, executed through inflammasome-driven gasdermin pore formation, and ferroptosis, mediated by iron-catalyzed lipid peroxidation upon GPX4 failure, have each been implicated in COPD pathogenesis but are conventionally treated as independent processes. This review advances three original contributions. First, we map pyroptotic and ferroptotic associations across COPD inflammatory endotypes, demonstrating preferential non-canonical pyroptotic engagement in T2-low neutrophilic disease and dual death-modality involvement in T2-high eosinophilic disease. Second, we delineate a hierarchical relationship—now supported in COPD-relevant epithelial systems—in which smoke-induced Nrf2 epigenetic silencing drives ferroptotic lipid peroxide accumulation that directly triggers pyroptotic execution through caspase-11 activation, positioning GPX4 as the molecular gatekeeper. Third, we propose an inverted U-shaped model reconciling paradoxical effects of lipid peroxidation on inflammasome regulation, where membrane phospholipid hydroperoxides drive activation while free cytosolic 4-hydroxynonenal mediates suppression through covalent NLRP3 modification. We further integrate extracellular trap biology as a convergent death-associated program sharing execution machinery with pyroptosis and ferroptosis. Building on this framework, we critically appraise emerging therapeutics—including dupilumab, anti-alarmin biologics, NLRP3 inhibitors, and ferroptosis-directed agents—and propose a biomarker-guided precision medicine strategy matching cell death-targeting therapies to individual inflammatory profiles. This framework reframes COPD therapeutic design from single-pathway inhibition toward integrated modulation of interconnected death programs stratified by inflammatory endotype.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1748748</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1748748</link>
        <title><![CDATA[The inhibition of the Aβ-ASC interaction site suppresses β-amyloid aggregation and cytotoxicity]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Lan Zhao</author><author>Xue Xia</author><author>Siqi Wang</author><author>Rui Liu</author><author>Zhenjiang Liu</author><author>Dong Sun</author><author>Xianghui Yu</author><author>Hui Wu</author>
        <description><![CDATA[Background and aimsThe deposition of β-amyloid (Aβ) in the cerebral cortex and hippocampus is a key pathological hallmark of Alzheimer’s disease (AD). Previous studies have shown that ASC specks released by activated microglia can bind to Aβ and promote its aggregation, thereby accelerating AD progression. However, the specific mechanisms underlying this interaction remain poorly understood. This study aims to identify the interaction sites between ASC and Aβ, design a vaccine targeting these sites, and evaluate its immunogenicity and therapeutic efficacy.MethodsThe interaction regions between ASC and Aβ were identified using pull-down and ELISA assays. Four types of nanoparticle carriers were purified using a prokaryotic expression system, and two peptides targeting the interaction sites were synthesized in vitro. These peptides were conjugated to the carriers via the SpyCatcher-SpyTag system. C57BL/6J mice were immunized with the constructed nanoparticles, and the immunogenicity of the vaccines was assessed by ELISA, while safety was evaluated by ELISpot. Serum antibodies were purified for further functional analysis.ResultsPull-down and ELISA results demonstrated that the C-terminal region of Aβ, particularly residues 29-42, and the pyrin domain (PYD) of ASC are key regions involved in binding. Eight nanoparticle vaccines carrying Aβ C-terminal epitopes were successfully prepared. Among them, the Ferritin-based Aβ vaccine induced a potent immune response targeting the Aβ-ASC interaction site without activating Aβ-specific T-cell responses. In vitro functional assays confirmed that the purified antibodies effectively disrupted Aβ-ASC binding, inhibited Aβ aggregation, and subsequently reduced its neurotoxicity.DiscussionOur findings indicate that the interaction site between ASC and Aβ is located within amino acids 29-42 of Aβ. Vaccines designed based on this site, Ferritin-Aβ29-35-3copy and Ferritin-Aβ36-42-3copy, effectively induced antibody production. The resulting antibodies suppressed Aβ aggregation and the neurotoxicity of Aβ oligomers. These data suggest that the Aβ-ASC interaction site may represent a potential target for AD therapy.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1792996</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1792996</link>
        <title><![CDATA[miRNA profiling shows shared signatures in pediatric asthma, obesity and their comorbidity]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Harshita Shailesh</author><author>Mohamed Nadhir Djekidel</author><author>Safa Noor</author><author>Lena Hayati</author><author>Stefan Worgall</author><author>Souhaila Al Khodor</author><author>Ibrahim Janahi</author>
        <description><![CDATA[RationaleChildhood obesity is a known risk factor for asthma and contributes to increased disease severity and reduced corticosteroid responsiveness. However, the molecular mechanisms underlying this comorbidity remain unclear. Using a cross-sectional design, we aimed to identify microRNA (miRNA) signatures associated with asthma–obesity comorbidity in children to shed light on potential shared molecular drivers.MethodsWhole blood samples were collected from four pediatric groups: normal weight with asthma (NW-A, n = 11), overweight/obesity with asthma (OO-A, n = 10), overweight/obesity without asthma (OO, n = 10), and normal weight without asthma (NW, n = 12). Circulating miRNA profiles were assessed using the NanoString nCounter platform. Differential expression and pathway enrichment analyses were performed using Enrichr and other bioinformatic tools. Correlation with clinical and cytokine data was assessed by Pearson’s correlation and multiple regression analyses.ResultsmiRNA expression profiles differed markedly across the four groups. Five miRNAs (miR- 423-3p, -92a-3p, -4536-5p, -197-3p, -891a-5p) were consistently upregulated, and two (miR-144-3p, -641) were downregulated across asthma alone, obesity alone, and asthma-obesity comorbidity. Target gene analysis of OO-A-associated miRNAs highlighted involvement in IL-4, IL-13, and PIP3/AKT signaling, as well as pathways linked to innate immunity and metabolism. In OO-A, miRNA dysregulation was correlated with elevated neutrophils, pro-inflammatory cytokines, and reduced lung function.ConclusionIn this exploratory study, we identified a shared circulating miRNA signature in asthma–obesity comorbidity. These miRNAs may serve as biomarkers and potential therapeutic targets for stratifying and managing asthma in children with obesity, pending validation in longitudinal studies.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1837640</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1837640</link>
        <title><![CDATA[Sex-specific reporting patterns and onset timing of immune-related adverse events associated with nivolumab and pembrolizumab: a dual-database pharmacovigilance analysis]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Yu Bai</author><author>Hong Liu</author><author>Hao Meng</author>
        <description><![CDATA[BackgroundNivolumab and pembrolizumab are associated with various immune-related adverse events (irAEs). However, sex-specific differences in irAE reporting patterns remain incompletely characterized, especially regarding timing of onset. Therefore, we conducted a dual-database pharmacovigilance study to evaluate the sex-specific reporting patterns and time-to-onset (TTO) of irAEs associated with nivolumab and pembrolizumab.MethodsThe U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases from 2014 to 2025 were used for the analyses. Eligible reports included those in which sex of a patient was known and nivolumab or pembrolizumab was recorded as a suspected drug. Sex-stratified disproportionality signals were assessed using multivariable logistic regression to estimate the adjusted reporting odds ratios, and sex differences in onset timing were evaluated using multivariable Weibull accelerated failure time models to estimate the adjusted time ratios.ResultsIn total, 146,796 eligible reports from FAERS and 56,767 from JADER were included. At the System Organ Class level, endocrine disorders showed consistent female-predominant reporting signals in both databases, whereas respiratory, thoracic, and mediastinal disorders showed consistent male-predominant patterns in both databases. At the individual irAE level, hypothyroidism and hyperthyroidism were the most prominent female-predominant signals, whereas interstitial lung disease was the most prominent male-predominant signal. TTO analysis results showed that endocrine disorders, especially hypothyroidism, occurred earlier in females than in males in both databases.ConclusionsThis study identified sex-associated patterns in endocrine and pulmonary irAEs related to nivolumab and pembrolizumab. However, our findings should be interpreted as signal-generating rather than causal, as they suggest that sex may be a clinically relevant factor in refining toxicity surveillance and individualized safety management during PD-1 inhibitor therapy.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1824573</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1824573</link>
        <title><![CDATA[Beyond the usual suspects: rethinking post-stroke immunosuppression]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Laia Ascaso-Vidal</author><author>Alba Simats</author><author>David Brea</author>
        <description><![CDATA[Ischemic stroke extends far beyond the hyperacute vascular event. In addition to the immediate ischemic injury, patients frequently develop systemic complications that significantly influence outcome. Among these, a biphasic immune response has emerged as a central feature: an early inflammatory reaction followed by a state of peripheral immunosuppression. This immunosuppressive phase has been consistently associated with increased susceptibility to post-stroke infections, particularly pneumonia, thereby contributing to morbidity and mortality. Multiple mechanisms have been implicated in the development of stroke-induced immunosuppression, including activation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, the release of damage-associated molecular patterns (DAMPs), reprogramming of bone marrow hematopoiesis, and peripheral neutrophil activation with downstream effects on lymphocyte survival. While these pathways are often studied in isolation, accumulating evidence suggests that they may interact within a coordinated neuroimmune network. In this review, we not only summarize the current understanding of the mechanisms underlying post-stroke immunosuppression but also explore how these processes may converge and influence one another. Finally, we discuss the unresolved question of whether this immunosuppressive state represents an adaptive response aimed at protecting the injured brain or a maladaptive bystander consequence of disrupted neuroimmune homeostasis.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1747043</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1747043</link>
        <title><![CDATA[Lactylation-mediated remodelling of the breast cancer microenvironment: single-cell multidimensional analysis and prognostic model construction]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Jiaxin Chen</author><author>Yixue Hao</author><author>Yinghua Feng</author><author>Yongjing Dai</author><author>Haoyuan Shi</author><author>Li Zhu</author>
        <description><![CDATA[BackgroundThe breast cancer tumour microenvironment (TME) exhibits marked cellular and metabolic heterogeneity that contributes to disease progression and therapeutic resistance. Lactylation, a lactate-derived post-translational modification, has emerged as a potential link between metabolic reprogramming and tumour-associated transcriptional and immune changes. However, its cell-type distribution and clinical relevance in breast cancer remain incompletely defined.MethodsWe integrated 26 scRNA-seq samples spanning ER+, HER2+, and triple-negative breast cancer (TNBC), comprising 98,572 cells. A literature-curated lactylation-related transcriptional module score was calculated using AddModuleScore, and epithelial cells were stratified into high- and low-score states for downstream analyses. Candidate genes were prioritised by integrating single-cell differential expression, a curated lactylation-related gene pool, and tumour-associated expression changes in TCGA-BRCA. A 14-gene prognostic model was developed using LASSO-Cox regression in TCGA-BRCA and externally validated in GSE20685 and METABRIC. Additional analyses evaluated associations with immune infiltration, somatic alterations, and predicted drug sensitivity. Functional relevance was explored through CALR knockdown in breast cancer cells and xenograft assays.ResultsSingle-cell analysis identified six major cell populations and revealed marked subtype-related heterogeneity. Lactylation-associated transcriptional activity was highest in epithelial cells, particularly in TNBC, and was associated with pathways related to immune response, cell cycle, and metabolic adaptation. High-score epithelial states showed enhanced epithelial–fibroblast–myeloid communication and were linked to an immune-modulatory microenvironment with partial immune-suppressive features. The 14-gene signature stratified patients into significantly different prognostic groups in TCGA-BRCA and retained prognostic value in GSE20685 and METABRIC. Internal resampling suggested modest but reproducible discrimination, although measurable optimism was observed in the training cohort. High-risk tumours were associated with distinct immune/stromal patterns, whereas mutation-frequency differences and tumour mutation burden did not show robust group differences after statistical correction. CALR knockdown suppressed proliferation, induced G1-phase arrest and apoptosis, and reduced xenograft growth.ConclusionsThis study defines a lactylation-associated transcriptional programme in breast cancer and links it to epithelial-state heterogeneity, microenvironmental remodelling, and patient prognosis. The proposed 14-gene signature may provide a transcriptome-based framework for risk stratification, but the findings should be interpreted cautiously because the lactylation score is an indirect surrogate rather than a direct measurement of lactylation itself. Further mechanistic and clinical validation will be required.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1834635</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1834635</link>
        <title><![CDATA[Clinical characteristics and long-term prognosis of talaromycosis in children with novel and reported inborn errors of immunity]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Qian Lu</author><author>Xianghui Li</author><author>Zhiwen Jiang</author><author>Tiantian Li</author><author>Bingkun Li</author><author>Lan Huang</author><author>Qihua Huang</author><author>Dongmei Hu</author><author>Chunying Lv</author><author>Guoqun Liu</author><author>Jialing Zhong</author><author>Jingjing Lin</author><author>Liuwei Liao</author><author>Qianfeng Qin</author><author>Sha Qin</author><author>Haotian Shao</author><author>Zhiyi Wang</author><author>Xiuying Li</author><author>Li Jiang</author><author>Xinyu Zhang</author><author>Lili Wei</author><author>Jiarong Liang</author><author>Dongyan Zheng</author><author>Shuangjie Wang</author><author>Weixuan Wu</author><author>Kaisu Pan</author><author>Yanqing Zheng</author><author>Yanning Li</author><author>Qing Tang</author><author>Min Jiang</author><author>Wanqing Liao</author><author>Cunwei Cao</author>
        <description><![CDATA[ImportanceLittle is known about the long-term prognosis of patients with talaromycosis and inborn errors of immunity (IEI).ObjectiveWe aimed to evaluate the clinical characteristics and long-term outcomes of talaromycosis in children with IEI on a 13-year cohort study.Main outcomes and measuresAn observational study was conducted on pediatric patients with talaromycosis at tertiary hospitals in southern China during 2012 to 2024. Data on demographic information, clinical features, immunological characteristics, genetic tests, antifungal treatment, and long-term prognosis were collected for analysis.ResultsAmong the 329 patients with talaromycosis without HIV, children accounted for 7%. 100% children with talaromycosis were diagnosed as IEI, and a total of 18 children were finally enrolled. All children were identified with IEI, including five novel genetic defects (IL7R, LYST, PLCG2, DOCK8, and KRAS deficiency) and five reported genetic defects (STAT1-GOF, IL2RG, CD40L, STAT3-LOF, CARD9 deficiency). Most children exhibited decreased lymphocytes, NK cells, and immunoglobulin levels. Half of children had been suffered from severe complications, such as sepsis or septic shock, thus had to received advanced life support in ICU. The median antifungal treatment duration was 16 months (IQR: 0.8-72.5 months). Amphotericin B and voriconazole are commonly used for induction therapy. Voriconazole and itraconazole are commonly used for maintenance therapy. Within 2 weeks of induction antifungal treatment, 3 patients died, and another 3 patients died within 24 weeks. At the end of observation, despite one child died of leukemia and one lost to follow-up, 4 achieved long-term relapse-free survival without antifungal treatment, and 6 were stable with maintenance antifungal therapy (One survived for more than 20 years, the longest recorded survival now). Most children benefited from immune boosting therapy, including 2 received HSCT intervention.Conclusions and relevanceTalaromycosis serves as an early warning indicator for IEI in HIV-uninfected children. Treatment and long-time management remain a challenge. Besides, long lasting anti-fungal and immune boosting therapy may be necessary, while HSCT intervention could provide potential benefits.]]></description>
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