Abstract
Cutaneous T-cell lymphomas (CTCLs) comprise a heterogeneous group of skin-homing T-cell malignancies with limited curative options. Recent genomic studies have identified recurrent alterations in tyrosine kinase signaling pathways in aggressive CTCL subtypes, particularly primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma (PCAETL) and primary cutaneous gamma/delta T-cell lymphoma (PCGDTL). Changes include kinase fusions and activating mutations involving JAK/STAT and FGFR pathways and provide a rationale for targeted therapy. Early clinical experience with tyrosine kinase inhibitors (TKIs) such as ruxolitinib, cerdulatinib, and pemigatinib demonstrated meaningful but frequently transient responses. Acquired resistance commonly arises through secondary kinase domain mutations, including canonical gatekeeper substitutions and cooperative mutations across paralogous kinases, with adverse events preventing continued treatment. Structural modeling supports steric interference and altered ATP affinity as key mechanisms limiting drug efficacy. Collectively, these findings reveal kinase addiction as a therapeutic vulnerability in selected CTCL subtypes but also underscore predictable adaptive resistance. Durable responses will likely require molecular stratification, longitudinal genomic monitoring, and local application of rational combination strategies. Aggressive CTCL thus represents a model for precision oncology in dermatology, where mechanistic insight can guide next-generation therapeutic approaches.
1 Introduction
Cutaneous T cell lymphomas (CTCLs) are a heterogenous group of clonal lymphoproliferative neoplasms affecting the skin. No curative treatment exists for CTCLs. While early-stage mycosis fungoides may remain indolent, several primary cutaneous cytotoxic T cell lymphomas are associated with poor survival. Primary cutaneous aggressive epidermotropic cytotoxic T cell lymphoma (PCAETL) and primary cutaneous gamma/delta T cell lymphoma (PCGDTL) are particularly challenging, with median survival commonly measured in months. Conventional systemic therapies, including allogeneic hematopoietic stem cell transplantation (), provide limited and often short-lived benefit. These therapeutic limitations have intensified efforts to define molecular drivers of aggressive CTCL. An urgent need for novel treatments remains.
Recent high-throughput genomic analyses have identified recurrent alterations in tyrosine kinase signaling pathways in PCAETL and PCGDTL, including kinase fusions and activating mutations involving JAK/STAT (janus kinase/signal transducer and activator of transcription) and FGFR (fibroblast growth factor receptor) pathways. Notably, high-throughput sequencing identified JAK2 and other kinase gene fusions (e.g. ABL1, FGFR1) in PCAETL (–) whereas PCGDTL frequently harbor activating mutations in the JAK/STAT pathway (, ). These discoveries have enabled the use of targeted tyrosine kinase inhibitors (TKIs) in select cases. Although responses can be dramatic, resistance frequently emerges. Toxicity can indirectly facilitate resistance by necessitating a dose reduction. Here we synthesize genomic, clinical and structural evidence to define mechanisms of acquired TKI resistance in primary cutaneous T cell lymphoma subtypes PCAETL and PCGDTL (–). A unifying framework of adaptive resistance emerges with implications for future therapeutic strategies.
2 Tyrosine kinase activation as a therapeutic vulnerability in PCAETL and PCGDTL
The therapeutic landscape of cutaneous T-cell lymphomas (CTCLs) has evolved with increasing recognition that aberrant kinase signaling is a key driver of disease progression and therapeutic resistance. Tyrosine kinase inhibitors (TKIs) have therefore emerged as a rational strategy to target dysregulated kinase pathways across CTCL subtypes. Early clinical studies evaluating TKIs in CTCLs, most notably PCAETL and PCGDTL, have demonstrated measurable clinical activity and underscore the potential of TKIs to achieve disease control in these highly aggressive lymphomas. The following sections summarize genetically defined therapeutic vulnerabilities in PCAETL and PCGDTL, current therapy approaches, and responses to TKI treatment.
2.1 Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma
Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma (PCAETL) was first recognized as an entity in 1999 based on its characteristic histopathologic and immunophenotypic features: epidermotropic CD8+ cytotoxic T cells expressing granzyme B, perforin, and/or TIA-1 (). Despite its rarity, PCAETL is among the most aggressive subtypes of CTCL with a median overall survival of 32 months and a 5-year survival of 31% (, ). PCAETL has a poor response to conventional therapies such as polychemotherapy, defining the need for molecularly informed treatments.
Recent genomic studies have revealed that PCAETL harbors recurrent and targetable kinase fusions. In one study, fusion genes involving JAK2 were detected in three of twelve patients () whereas another study reported kinase gene fusions in six of six PCAETL samples: five harbored a JAK2 fusion, and one carried a novel ABL1 fusion (). Another report showed a kinase gene fusion in PCAETL fusing SATB1 to FGFR1, a receptor tyrosine kinase for fibroblast growth factors (FGFs) (). In all cases, the tyrosine kinase domains are conserved at the C-terminus and are fused to a plethora of genes including STAT3, KHDRBS1, PICALM, CAPRIN1, SELENO, PCM1, and TFG. The biological basis for the recurrent involvement of JAK2, rather than other JAK family members typically utilized by CD8+ T cells (including JAK1 and JAK3) remains unknown. This preferential JAK2 involvement may reflect lineage infidelity, with transformed CD8+ T cells deviating from canonical cytokine signaling to exploit JAK2-mediated proliferative or survival pathways. These findings suggest that JAK2 may play a unique role in driving oncogenic signaling in PCAETL.
While JAK2 fusions represent the most common genetic alteration in PCAETL, other kinase fusions have been described. A recent case involving a SATB1-FGFR1 fusion demonstrated a meaningful response to the FGFR inhibitor, pemigatinib (). The patient achieved almost 90% regression of ulcerated lesions and maintained partial remission for four months on pemigatinib (). However, pemigatinib dose reduction due to toxicity led to relapse, and subsequent sequencing revealed an acquired FGFR1 kinase domain mutation conferring resistance (). The patient expired two months later ().
This case represents the first reported clinical use of a TKI in PCAETL, underscoring both the therapeutic potential and challenges of targeting kinase fusions in CTCLs. The emergence of resistance mechanisms, such as secondary kinase domain mutations, highlights the need for longitudinal molecular monitoring and rational therapeutic strategies to improve outcomes in this rare, aggressive lymphoma subtype.
2.2 Primary cutaneous gamma/delta T-cell lymphoma
Primary cutaneous gamma delta T cell lymphoma (PCGDTL) is a rare and highly aggressive subset of CTCL characterized by clonal proliferation of mature, activated γδ T cells. Patients with PCGDTL have a median overall survival of approximately 31 months and a 5-year disease-specific survival of only 19.9% (). Unlike PCAETL, PCGDTL shows variable infiltration, ranging from epidermotropic to predominantly subcutaneous patterns. Notably, clinical and histopathologic features correlate with TCR δ-chain usage: epidermal/dermal cases typically express TRVδ1, while subcutaneous cases express TRδV2 (). Despite this correlation, NGS analyses have not identified major mutational differences between these subsets. Instead, PCGDTL is characterized by marked genomic instability, with a median of 166.5 somatic copy number variants per sample (). Nevertheless, recurrent alterations have been identified in key oncogenic signaling pathways. Putative driver mutations involved genes within the MAPK signaling pathway (KRAS, NRAS, MAPK1), the MYC pathway (MYC, MYCN, FBXW7), and the JAK/STAT pathway (STAT3, STAT5B, JAK3, SOCS1) (). Among these, KRAS mutations were most common, while approximately 21% of samples harbored JAK/STAT point mutations ().
A recent case study expanded the understanding of recurrent point mutations in PCGDTL. One patient harbored a SOCS1 (negative regulator of JAK/STAT signaling) deletion, while another carried a JAK3 point mutation (p.A573V) within the pseudokinase domain (), a mutation previously identified in natural killer T-cell lymphoma (). Notably, tumor cells from both patients expressed TRVδ1. The SOCS1-deleted patient was treated with JAK1/2 inhibitor ruxolitinib and initially achieved near-complete regression (). However, disease progression occurred after 8 weeks, accompanied by new lesions (). Next-generation sequencing of the relapse sample revealed a newly acquired STAT5B p.N642H mutation, a well-characterized driver mutation associated with T-cell neoplasms and drug-resistant leukemias ().
The patient with JAK3 p.A573V was enrolled in a phase II clinical trial evaluating the dual spleen tyrosine kinase (SYK) and JAK inhibitor cerdulatinib (). After 7 weeks of treatment, the patient experienced an 86% reduction in skin disease burden; however, therapy was discontinued due to adverse events (). Shortly after, disease relapse occurred, and subsequent biopsy revealed the acquisition of JAK3.pM511I, JAK1 p.L783F, and a JAK1 p.T901A mutation in circulating tumor cells (). Like the FGFR1 fusion positive PCAETL case, these findings underscore a pattern of initial sensitivity to TKIs followed by emerging secondary mutations conferring resistance.
3 Mechanisms of acquired resistance in PCAETL and PCGDTL
Despite initial clinical responses to TKIs, durable remissions remain uncommon across PCAETL and PCGDTL. Resistance to TKIs in PCAETL and PCGDTL arises through diverse mechanisms, including secondary mutations within drug-binding pockets. Understanding these mechanisms is critical for guiding the development of regimens aimed at overcoming or preventing resistance.
3.1 Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma
In the study identifying the SATB1-FGFR1 fusion in PCAETL, two secondary mutations- E462V and V561L- were detected in FGFR1 following pemigatinib treatment (). The E462V substitution lies within the juxtamembrane region, whereas V561L occurs in the kinase domain and represents a canonical gatekeeper mutation. The juxtamembrane region of FGFR1 mediates interactions with several adaptor proteins and serves as a critical signaling hub that couples FGFR1 to multiple intracellular pathways. Despite its location, the E462V mutation in SATB1-FGFR1 did not confer resistance to pemigatinib (), suggesting that this substitution may not disrupt the interactions required for downstream MAPK and PI3K activation. Indeed, through structural modeling, E462V was not found to cause clashes or modulate the drug-binding state (Figure 1A).
Figure 1
In contrast, the V561L mutation within the kinase domain represents a well-characterized gatekeeper mutation that sterically impedes inhibitor binding and enhances ATP affinity, thereby reducing TKI potency (). Structural modeling of a substitution at the same residue (V561M) revealed that replacement with a bulky methionine side chain induces steric clashes within the inhibitor-binding pocket, accounting for the observed resistance (). Structural modeling of V561L shows similar results, inducing steric clashes and destabilizing drug binding (Figure 1A). This mutation has been previously described in FGFR1-driven myeloproliferative neoplasms, where it confers broad resistance to multiple FGFR inhibitors (). Although pemigatinib has demonstrated clinical activity in FGFR-rearranged malignancies (), the emergence of gatekeeper mutations such as V561L underscores the adaptive capacity of FGFR-driven malignancies and highlights the need for next-generation FGFR inhibitors or combinational strategies to prevent or overcome resistant clones.
3.2 Primary cutaneous gamma/delta T-cell lymphoma
Acquired resistance to targeted therapies in cytotoxic T-cell malignancies, including PCGDTL, can arise through diverse mechanisms such as secondary kinase mutations and aberrant JAK/STAT signaling. In contrast, pre-existing alterations like SOCS1 deletion are particularly interesting in PCGDTL, given SOCS1`s well-established role in immune cell differentiation and regulation, especially in γδ T cells (). A recent case study underscores the contribution of SOCS1 loss, describing the first reported case of SOCS1-deficient PCGDTL treated with the JAK1/2 inhibitor ruxolitinib ().
In the PCGDTL case, the patient initially responded to ruxolitinib, with aberrant IL-2/STAT5 signaling observed in tumor cells relative to normal γδ T cells (). However, the patient ultimately relapsed and acquired a STAT5B p.N642H mutation (). This well-characterized gain-of-function mutation occurs in the Src homology 2 (SH2) domain of STAT5B and has been reported in multiple leukemia and lymphoma cases. It stabilizes STAT5B dimers, increases phosphorylation, and renders the protein constitutively active (). Structural studies indicate that p.N642H alters the hydrogen-bonding network within the phosphotyrosine pocket, favoring inter-protein interactions in the STAT5B dimer (). These findings strongly suggest that the STAT5 p.N642H mutation drove acquired resistance to JAK inhibition, illustrating how pre-existing tumor suppressor loss and secondary activation mutations can converge to limit treatment durability.
In the same study, another PCGDTL patient initially harbored a JAK3 p.A573V point mutation and presented with a one-year history of plaques and nodules (). The patient was subsequently enrolled in a phase II clinical trial of the dual SYK/JAK inhibitor cerdulatinib, which initially reduced skin disease burden (). However, after 16 weeks of treatment, new tumors arose and the JAK3 mutation was detected in peripheral blood, indicating leukemic progression. Next-generation sequencing of post-relapse tumor and blood samples identified additional acquired mutations: JAK3 p.M511I in the tumor, and JAK1 p.L783F and JAK1 p.T901A in peripheral blood ().
Both JAK3 p.A573V and JAK3 p.M511I have been previously reported, including in T-cell acute lymphoblastic leukemia (T-ALL), where up to one-third of cases exhibit biallelic mutations affecting these residues (). Either mutation alone can activate JAK3 kinase activity (). M511 lies within the SH2-pseudokinase (JH2) linker, which typically interacts with the kinase domain active site. The M511I mutation destabilizes this linker, promoting activation of the kinase domain (). In contrast, A573 is located within the αC helix of the pseudokinase domain- a key structural element that toggles between active and inactive conformations. Structural modeling of the mutations has been reported and suggests that the combination of M511I and A573V may lead to stronger JAK3 activation, but these mutations have not been modeled with a JAK inhibitor. Through structural modeling of the mutants with cerdulatinib, the M511I and A573V mutations cause steric hindrance (Figure 1B). This suggests the variants confer resistance to cerdulatinib by inter- or intramolecular interaction alterations.
The JAK1 p.L783F mutation has also been identified in T-ALL (), although its functional role remains unclear. This residue lies within the JH2 linker, and in the PCGDTL case, the combined presence of JAK3 p.A573V and JAK1 p.L783F conferred greater resistance to cerdulatinib compared to single mutants (), indicating cooperative resistance (). Interestingly, these mutations occur in different JAK family members, raising important questions about how cross-kinase cooperation contributes to drug resistance in PCGDTL. Structural modeling of JAK1 p.L783F with cerdulatinib shows steric hindrance (Figure 1C). Lastly, the JAK1 p.T901A mutation also reported in T-ALL has been associated with steroid resistance and shows lower overall survival compared to patients with wild type JAK1 ().
Together, these findings underscore how pre-existing and therapy-induced mutations within the JAK/STAT pathway shape disease progression and therapeutic resistance in PCGDTL, highlighting the need for combination or next-generation JAK inhibitors capable of overcoming these adaptive mechanisms.
4 Adverse events of tyrosine kinase inhibitors in PCAETL and PCGDTL
The selectivity of tyrosine kinase inhibitors (TKIs) largely dictates the compound`s potency, mechanism of action, and safety profile. Although some TKIs exhibit high specificity, most possess broader activity across multiple kinases, thereby increasing the risk of off-target effects (). Adverse events (AEs) may arise from excessive on-target inhibition within normal tissues or off-target effects with other signaling pathways. The following section reviews the adverse effects associated with TKI inhibition in PCAETL and PCGDTL, highlighting shared patterns of toxicity.
4.1 Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma
In a patient harboring a SATB1-FGFR1 fusion, treatment with FGFR inhibitor pemigatinib led to a remarkable initial response, with approximately 90% improvement after two weeks of therapy and partial remission for around four months (). However, the patient experienced AEs including hyperphosphatemia, nail changes, and ocular irritation, necessitating a dose reduction (). The patient`s lesions then relapsed within one month and sequencing revealed secondary point mutations within the FGFR1 kinase domain. Whether these mutations emerged as a consequence of reduced drug exposure, selection of a resistant subclone, or through intrinsic tumor adaptation remains unclear.
Nevertheless, treatment-related toxicities to pemigatinib remain a major limitation. The most common reported AEs to pemigatinib include hyperphosphatemia, nail toxicity, alopecia, diarrhea, anemia, dry eyes, and serous retinal detachment (). These AEs reflect the broad physiological role of FGFR signaling, as FGFRs are expressed in the corneal epithelium, photoreceptors, iris, and hair follicles (), consistent with the ocular and dermatological patient manifestations. The SATB1-FGFR1 patient underscores the clinical challenge of balancing efficacy and tolerability, as dose reductions necessitated by toxicity may inadvertently promote the emergence of resistant subclones.
4.2 Primary cutaneous gamma/delta T-cell lymphoma
Similar to the SATB1-FGFR1 case, PCGDTL case studies involving JAK/STAT pathway inhibition demonstrated transient clinical responses followed by relapse and the acquisition of secondary mutations (). In one patient with SOCS1 loss, treatment with ruxolitinib, a JAK1/2 inhibitor, resulted in near-complete regression after four weeks (). However, after eight weeks, the disease progressed rapidly, highlighting the limited durability of response.
Ruxolitinib has been evaluated in a phase II clinical trial in 53 patients with CTCL. Reported toxicities were consistent with its established safety profile and included anemia (15/53), diarrhea (7/53), thrombocytopenia (9/53), and neutropenia (10/53) (). These AEs reflect the critical role of JAK/STAT signaling in normal hematopoiesis and immune homeostasis (). In particular, JAK2 signaling is essential for erythropoietin and thrombopoietin receptor function, explaining the frequent development of cytopenias with JAK2 inhibition (). Accordingly, ruxolitinib has been shown to induce dose-dependent myelosuppression and thrombocytopenia (, ), attributable to both on target JAK2 inhibition and direct effects on hematopoietic progenitor cells.
In another PCGDTL case, treatment with cerdulatinib, a dual SYK and JAK inhibitor, produced an 86% reduction in skin tumor burden in a patient harboring a JAK3 p.A573V mutation (). However, treatment was discontinued after 7 weeks due to grade 3 AEs. By 16 weeks, the disease recurred with new lesions, and sequencing revealed acquired mutations in JAK1 and JAK3 (), both sufficient to confer resistance to cerdulatinib.
Consistent with this case, a phase II clinical trial of cerdulatinib in relapsed/refractory peripheral T-cell lymphoma and CTCL reported frequent grade >3 AEs including increased lipase (29.2%), increased amylase (43.1%), diarrhea (43.1%), and anemia (32.3%) (). Serious AEs occurred in 64.6% of patients, most commonly neoplasm progression (20%), sepsis (9.2%), pyrexia (7.7%), and pneumonia (4.6%) (). Tragically, two deaths not related to disease progression were attributed to cerdulatinib ().
Mechanistically, cerdulatinib targets members of the SYK and JAK families- excluding JAK2. SYK is a non-receptor tyrosine kinase containing two SH2 domains and a kinase domain and is highly expressed in hematopoietic cells (). While this dual inhibitory activity may underlie its potent antitumor effects, it also likely contributes to the significant toxicity profile, making cerdulatinib a challenging option for long-term therapy, particularly where relapse occurs soon after discontinuation due to AEs.
5 Discussion
Collectively, the genomic and clinical data across PCAETL and PCGDTL underscore a unifying theme: aberrant kinase signaling (most notable through JAK/STAT and FGFR pathways) is a key pathogenic driver and therapeutic vulnerability in PCAETL and PCGDTL. The discovery of recurrent kinase mutations and fusions, including JAK2 and FGFR1 rearrangements reveals that subsets of these lymphomas are mechanistically dependent on constitutive kinase activity for survival and proliferation. Early-phase clinical trials and case reports demonstrate that targeted inhibition using TKIs such as ruxolitinib, cerdulatinib, and pemigatinib can yield meaningful though often transient clinical responses, limited by emerging resistance mechanisms (Figure 2). These findings emphasize the need for molecular stratification of patients based on kinase dependency and the development of next-generation inhibitors with improved potency and resistance profiles.
Figure 2
To achieve durable responses and prevent drug resistance, future therapeutic strategies will require expanding beyond single-agent TKI therapy toward rational combination regimens, while topical application might circumvent a need for reduced dosing and provide a window for prolonged therapeutic efficacy (, ). Preclinical and clinical evidence across malignancies supports the potential of combining TKIs with immune checkpoint blockade. For example, the JAK1 inhibitor itacitinib has been evaluated in combination with pembrolizumab, a monoclonal antibody against PD-1, in non-small cell lung cancer (NSCLC) (). Here itacitinib was introduced following two cycles of pembrolizumab, the standard of care in NSCLC. Approximately two-thirds of patients ultimately relapse after pembrolizumab alone (). The combination was designed to counteract upregulation of interferon-stimulated genes found in relapsed NSCLC, and encouragingly, the 12-week overall response rate was 62%, with a median progression-free survival of 23.8 months ().
Similarly, an early phase I clinical trial explored the use of a JAK inhibitor in combination with an anti-PD-1 antibody in Hodgkin lymphoma patients who relapsed or were refractory after prior checkpoint inhibitor therapy (). In this study, ruxolitinib was administered with nivolumab, yielding an overall response rate of 53%. Mechanistically, ruxolitinib appeared to rescue exhausted T cells and demonstrated synergy with nivolumab in reshaping the myeloid compartment, thereby enhancing both NK and T cell responses (). Although no clinical trials have yet evaluated checkpoint inhibitor-TKI combinations in aggressive T cell lymphomas, such approaches may warrant investigation given their aggressive and immune-evasive nature.
In conclusion, aggressive CTCL subtypes such as PCAETL and PCGDTL demonstrate actionable kinase alterations for meaningful targeted therapy. However, adaptive resistance through kinase mutations is common. Future progress relies on molecular stratification, longitudinal genomic monitoring, rational combination therapy, and development of mutation-selective next-generation inhibitors. Aggressive CTCL thus presents both a challenge and an opportunity for precision dermato-oncology.
Statements
Author contributions
JY: Writing – review & editing, Writing – original draft, Visualization, Conceptualization. CB: Writing – review & editing. AG: Writing – review & editing. JG: Writing – review & editing. CT-C: Writing – review & editing. IP: Writing – original draft, Supervision, Writing – review & editing. XZ: Supervision, Writing – original draft, Writing – review & editing.
Funding
The author(s) declared that financial support was received for this work and/or its publication. NCI 5R01CA260064 to CLP.
Conflict of interest
AG reports editorial roles as Specialty Chief Editor for Frontiers in Drug Discovery – Dermatologic Drugs, Associate Editor for the Journal of Investigative Dermatology and the International Journal of Dermatology; service as Physician Editor for VisualDx; membership on the Board of Directors for the Biology of Skin Foundation; and employment as Senior Medical Director at AbbVie, all outside the submitted work. CGB has served as an investigator and/or consultant for AbbVie, Almirall, Alumis, Amgen, Apogee, Arcutis, Botanix, Castle Biosciences, Connect BioPharma, Daiichi Sankyo, Dermavant, Disc Medicine, Eli Lilly, EPI Health/Novan, Galderma, Incyte, LEO Pharma, Novartis, Ortho Dermatologics, Palvella, Pfizer, Regeneron, Sanofi, South Beach Symposium, Sun Pharma, Takeda, Timber, Teladoc, Triveni, UCB, and Veradermics, all outside the submitted work. CLP reports roles as CSO and CIO, respectively of Northwestrn spinoff companies Temprian Therapeutics and Tempian Oncology, respectively and a consulting role for Janssen Pharmaceuticals, all unrealted to the current work.
The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Abbreviations
CTCLs, cutaneous T-cell lymphomas; TKIs, tyrosine kinase inhibitors; STAT, signal transducer and activator of transcription; JAK, janus kinase; PCGDTL, primary cutaneous gamma delta T-cell lymphoma; PCAETL, primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma; WGS, whole genome sequencing; RNA-seq, RNA-sequencing; SOCS, suppressor of cytokine signaling; FGFR, fibroblast growth factor receptor; AEs, adverse events
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Summary
Keywords
secondary mutation, cutaneous T cell lymphoma, FGFR inhibitor, gamma delta T (γδ T) cells, JAK inhibition, kinase signaling, treatment resistance, tyrosine kinase inhibition
Citation
Yescas JA, Bunick CG, Grada A, Guitart J, Torres-Cabala CA, Le Poole IC and Zhou XA (2026) Mechanisms of kinase inhibitor resistance in subtypes of cutaneous T-cell lymphomas. Front. Hematol. 5:1812908. doi: 10.3389/frhem.2026.1812908
Received
17 February 2026
Revised
16 April 2026
Accepted
17 April 2026
Published
13 May 2026
Volume
5 - 2026
Edited by
Andrea Visentin, University of Padua, Italy
Reviewed by
Aquib Ehtram, La Jolla Institute for Immunology (LJI), United States
Updates
Copyright
© 2026 Yescas, Bunick, Grada, Guitart, Torres-Cabala, Le Poole and Zhou.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Julia A. Yescas, julia.yescas@northwestern.edu; I. Caroline Le Poole, caroline.lepoole@northwestern.edu
†These authors have contributed equally to this work
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.