Abstract
Head and neck squamous cell carcinoma (HNSCC) remains a clinically challenging malignancy due to its intratumoral heterogeneity, aggressive progression, and resistance to multimodal treatment. Extracellular vesicles (EVs)—including exosomes and microvesicles—have gained attention as active contributors to these phenotypes by mediating intercellular signaling and molecular cargo transfer. HNSCC-derived EVs carry oncogenic and drug resistance proteins, along with microRNAs that promote immune evasion and EMT. Enrichment of microRNAs including miR-21, miR-214, and miR-221/222 within EVs supports angiogenesis, apoptosis evasion, and immune suppression. EV-associated PD-L1 impairs antigen presentation and T cell activity, contributing to resistance to checkpoint blockade. Additionally, EVs promote epithelial-to-mesenchymal transition and extracellular matrix remodeling, facilitating invasion and pre-metastatic niche formation. Through modulation of T cell function, macrophage polarization, and stromal recruitment, EVs help establish an immune-tolerant microenvironment. This review synthesizes current knowledge on the mechanistic roles of EVs in HNSCC and discusses their potential as diagnostic biomarkers and therapeutic targets.
1 Introduction
Therapeutic resistance is a pervasive challenge in oncology, accounting for the vast majority of treatment failures in metastatic cancers (1, 2). This resistance emerges from a multifactorial network involving genetic mutations, epigenetic alterations, and microenvironmental influences. Increasingly, extracellular vesicles (EVs) have gained attention as critical mediators of this process (3, 4). These lipid bilayer-enclosed vesicles—secreted by diverse cell types including tumor, stromal, immune, and platelet-derived cells—serve as carriers of bioactive molecules such as proteins, microRNAs, mRNAs, long non-coding RNAs, and fragments of oncogenic DNA (5, 6). By transferring this molecular cargo, EVs facilitate both autocrine and paracrine communication, reprogramming recipient cells and reshaping the tumor microenvironment (TME) to support angiogenesis, immune evasion, metabolic adaptation, and metastasis.
Of particular interest is the role of EVs in undermining anti-tumor immunity and promoting resistance to immunotherapy. In this context, EV-associated PD-L1 can be delivered to T cells and antigen-presenting cells, inducing T cell exhaustion and functional impairment (7–9). Additionally, EVs transport resistance-associated molecules such as ATP-binding cassette (ABC) transporters, anti-apoptotic proteins like Bcl-2, and regulatory microRNAs that collectively suppress apoptosis, enhance DNA repair mechanisms, and facilitate drug efflux (3, 10, 11). These vesicles can also impair antigen presentation and downregulate MHC expression, contributing to the development of an immunologically “cold” tumor microenvironment, even in the presence of immune checkpoint blockade (6, 12, 13).
Head and neck squamous cell carcinoma (HNSCC), a malignancy originating from the mucosal surfaces of the oral cavity, pharynx, and larynx, exemplifies the clinical impact of EV-mediated resistance. Despite aggressive, multimodal treatment strategies—including surgery, radiation, chemotherapy, and immunotherapy—survival rates remain poor for patients with advanced disease (14–16). HNSCC is characterized by a highly immunosuppressive and heterogeneous TME, displaying a spectrum from immune-inflamed to immune-excluded or desert phenotypes (17, 18). These features, coupled with the tumor’s inherent genomic instability and adaptability, make HNSCC a particularly valuable model for studying the functional and translational implications of EVs (17, 19).
This narrative review aims to synthesize current knowledge on the role of extracellular vesicles in HNSCC, with a focus on their contribution to immune modulation and therapy resistance (Figure 1). We begin by outlining EV biogenesis, classification, and cargo profiles (Table 1). We then explore the mechanisms by which HNSCC-derived EVs influence tumor progression, immune escape, and resistance to treatment. Finally, we examine emerging therapeutic strategies targeting EVs and discuss future directions for leveraging EV biology to improve outcomes in HNSCC.
Figure 1
Table 1
| EV Methods | Technique | Key features | Strengths | Limitations | Recommended use |
|---|---|---|---|---|---|
| EV Isolation Methods | Differential Ultracentrifugation | Commonly used for EV isolation; relatively simple. | Widely available; cost-effective for large-scale isolation. | Can lead to contamination with non-EV particles; time intensive. | Recommended for bulk EV isolation in research settings where high yield is prioritized over purity. |
| Size-Exclusion Chromatography (SEC) | Separates EVs based on size without harsh processing. | Maintains EV integrity; minimal processing artifacts. | Limited scalability; may co-isolate non-EV macromolecules. | Ideal for preserving EV integrity in functional assays and downstream molecular studies. | |
| Immunoaffinity Capture | Enables selective isolation of specific EV subtypes. | High specificity for targeted EV subpopulations. | Low yield; potential bias in subtype enrichment. | Best suited for targeted studies on specific EV subpopulations or biomarker discovery. | |
| EV Characterization Methods | Nanoparticle Tracking Analysis (NTA) | Measures EV size distribution and concentration using light scattering. | High throughput; provides quantitative data on EV concentration. | Lacks specificity in distinguishing EV subtypes. | Appropriate for routine size and concentration profiling of EV samples. |
| Dynamic Light Scattering (DLS) | Provides size distribution based on Brownian motion. | Simple, rapid, and requires minimal sample preparation. | Poor resolution for polydisperse EV populations. | Useful for quick, preliminary size estimation of monodisperse EV samples. | |
| Transmission Electron Microscopy (TEM) | High-resolution imaging of EV morphology. | Provides detailed visualization of EV structure and morphology. | Requires extensive sample preparation; lacks molecular composition data. | Recommended for morphological validation and structural analysis of isolated EVs. | |
| Flow Cytometry | Enables single-vesicle analysis of surface markers. | Allows phenotypic characterization of EV subpopulations. This includes specific kits (beads) for exosome surface marker labeling. | The availability and validation of high-quality antibodies against specific EV markers are still limited. | Optimal for identifying and quantifying surface markers on EV subtypes. | |
| Proteomics, Transcriptomics, Lipidomics | Provides detailed molecular profiling of EV cargo. | High-resolution molecular characterization; identifies EV biomarkers. | Requires high-purity EV preparations and advanced bioinformatics analysis. | Best used in comprehensive omics studies for biomarker discovery or cargo profiling. |
Summary of commonly used techniques for EV isolation and characterization, highlighting key features, strengths, and limitations.
These methods vary in specificity, resolution, scalability, and compatibility with downstream analyses, influencing their suitability for different research and clinical applications.
2 Extracellular vesicles in HNSCC: mechanisms of tumor progression, immune evasion, and therapeutic resistance
2.1 Biogenesis and classification of EVs in HNSCC
EVs in HNSCC include exosomes, microvesicles, and apoptotic bodies, which differ in biogenesis and molecular signature but collectively act as powerful modulators of tumor progression. Exosomes (30–150 nm), originating from multivesicular bodies via ESCRT-dependent and independent pathways, are enriched in HNSCC with markers like ALIX, TSG101, and tetraspanins, and play a central role in immune suppression through PD-L1 delivery (5, 20, 21). Microvesicles (100–1000 nm), formed by membrane budding and cytoskeletal rearrangement, are particularly enriched in chemoresistant HNSCC cells and carry functional efflux pumps such as P-glycoprotein and DNA repair proteins like ERCC1 (3, 4, 17). Apoptotic bodies (1000–5000 nm), once thought to be inert debris, are now recognized as potential vectors for DAMPs and oncogenic DNA, contributing to the evolution of resistance and intratumoral heterogeneity in HNSCC (4, 5, 22–24). In summary, the classification and cellular origin of EVs in HNSCC directly shape their diverse functional roles in therapy resistance, immune modulation, and tumor adaptation (Table 2).
Table 2
| Feature | Exosomes | Microvesicles (MVs) | Apoptotic bodies |
|---|---|---|---|
| Size Range | 30–150 nm | 100–1,000 nm | 500–2,000 nm |
| Biogenesis | Intraluminal budding of multivesicular bodies (MVBs); released via exocytosis | Direct outward budding of plasma membrane | Fragmentation of apoptotic cells |
| Release Trigger | Constitutive or induced by stress | Cellular activation, stress | Programmed cell death (apoptosis) |
| Markers | CD9, CD63, CD81, TSG101, Alix | ARF6, Annexin A1, Integrins, Selectins | Histones, fragmented DNA, phosphatidylserine |
| Cargo Composition | Enriched in miRNAs, tRNAs, mRNAs, proteins (e.g., heat shock proteins), lipids | Similar to parent cell; includes proteins, RNAs, lipids | Nuclear fragments, organelles, DNA, and proteins |
| Function | Intercellular communication, immune modulation, angiogenesis | Signal transmission, coagulation, immune activation | Clearance of cellular debris, immune modulation |
| Isolation Challenges | Small size complicates separation from lipoproteins | Heterogeneity, overlaps with exosomes | Often mixed with larger EVs or cell debris |
| Detection Methods | NTA, TEM, Western blot (CD63+, CD81+) | Flow cytometry, DLS, TEM | Microscopy, flow cytometry |
Comparative overview of extracellular vesicle (EV) subtypes.
This table summarizes key distinguishing features of the three main EV subtypes—exosomes, microvesicles (MVs), and apoptotic bodies. It outlines differences in size range, mechanisms of biogenesis, stimuli for release, surface markers, cargo composition, and biological functions. Additionally, it highlights practical challenges in isolation and commonly used detection methods for each subtype. Understanding these distinctions is critical for accurate characterization and application of EVs in both research and clinical contexts.
2.2 Molecular cargo and oncogenic signatures of HNSCC-derived EVs
HNSCC-derived EVs contain a distinctive and functionally potent cargo profile that drives tumor growth and immune modulation. Proteomic analyses confirm enrichment of receptor tyrosine kinases (e.g., EGFR), heat shock proteins (HSP70, HSP90), and ATP-binding cassette transporters (MRP1, ABCG2), all of which support survival signaling and resistance to targeted and cytotoxic therapies (10, 11, 17). In addition, EVs from HNSCC tumors frequently carry DNA repair enzymes such as ERCC1 and XRCC1, enabling recipient cells to better withstand platinum-based chemotherapy (15, 25, 26). Regulatory microRNAs are another key cargo class; miR-21, miR-214, and miR-221/222 are consistently enriched in tumor-derived EVs and modulate gene expression to suppress apoptosis, enhance angiogenesis, and promote invasion (19, 27, 28). These miRNAs exert their effects through well-characterized signaling axes: for example, miR-21 suppresses PTEN, leading to activation of the PI3K-AKT pathway and enhanced cell survival, while miR-221/222 target both PTEN and TIMP3 to promote migration, EMT, and matrix remodeling. In support of this, plasma-derived small EVs (sEVs) from HNSCC patients have been shown to strongly enhance angiogenic potential, underscoring their systemic bioactivity and functional relevance beyond the local tumor microenvironment (29).
2.3 EV-mediated mechanisms of resistance in HNSCC
In HNSCC, EVs serve as mobile vectors of resistance, particularly in the context of cisplatin therapy. Exosomes and microvesicles from resistant HNSCC cells are enriched with ERCC1 and XRCC1, which facilitate nucleotide and base excision repair, thereby neutralizing the cytotoxic effects of DNA-damaging agents (15, 17, 30, 31). These vesicles also carry high levels of HSP70 and HSP90, which stabilize DNA repair proteins and stress-response effectors, further enhancing survival under chemotherapeutic pressure (17). Notably, field cancerization in HNSCC allows EVs to transmit resistance phenotypes across spatially distinct tumor foci, fostering a functionally resistant network (4, 5, 26). Moreover, the presence of anti-apoptotic proteins like Bcl-2 in radioresistant HNSCC-derived EVs confirms their role in shielding cells from radiation-induced cell death (32). Overall, EVs in HNSCC orchestrate a multifaceted resistance network that undermines therapeutic efficacy across both clonal populations and anatomical compartments.
2.4 EV-induced EMT and metastatic reprogramming in HNSCC
EVs in HNSCC actively drive epithelial-mesenchymal transition (EMT), a key program in metastasis and immune evasion. Tumor-derived EVs transport transcriptional repressors such as Snail and β-catenin, which suppress epithelial markers (e.g., E-cadherin) and upregulate mesenchymal traits (e.g., vimentin, N-cadherin), promoting migratory and invasive capacities (33–36). These EVs also deliver MMP1, MMP3, and integrins (ITGA6, ITGB1), which degrade the extracellular matrix and enable pre-metastatic niche formation—processes particularly relevant in high-grade HNSCC (23, 37). Recent findings have shown that plasma-derived sEVs can reprogram macrophages to facilitate pre-metastatic niche formation in HNSCC, emphasizing their role in priming distant sites for metastatic colonization (38). Furthermore, EVs contain annexins and galectin-3-binding protein (LGALS3BP), which contribute to stromal reprogramming and immune cell dysfunction (39–42). Thereby, EV-driven EMT in HNSCC fosters a dual threat of immune escape and enhanced invasiveness, positioning EVs as central regulators of metastatic evolution.
2.5 Immunosuppressive functions of EVs in the HNSCC microenvironment
HNSCC-derived EVs are potent immunosuppressive agents that sculpt a TME conducive to tumor persistence and immune escape. Additionally, miR-27a within these vesicles targets immune-activating genes, suppressing co-stimulatory molecule expression in dendritic cells and macrophages (43, 44). EVs also act as antigen decoys, shedding tumor-associated antigens (TAAs) to divert immune recognition while displaying surface CD47 to inhibit macrophage-mediated clearance (45, 46). Moreover, HNSCC EVs secrete TGF-β and IL-10, driving Treg expansion and M2 macrophage polarization, both of which contribute to a tolerogenic and therapy-resistant microenvironment (6, 13). In summary, EVs play a pivotal role in HNSCC immune evasion by blunting anti-tumor immunity and engineering an immune landscape hostile to therapeutic response. The diverse immunosuppressive, pro-metastatic, and resistance-promoting functions of EVs in HNSCC are summarized in Figure 2.
Figure 2
2.6 Integrative role of EVs in HNSCC progression and therapeutic resistance
Extracellular vesicles in HNSCC serve as multifaceted conduits of tumor adaptation, orchestrating molecular, cellular, and systemic changes that reinforce malignancy. By transferring oncogenic and resistance-associated cargo, EVs orchestrate interactions between tumor, stromal, and immune compartments that reinforce therapeutic failure (2, 3, 5, 17). Moreover, the capacity of EVs to cross anatomical and histological boundaries through lymphatic and circulatory systems makes them ideal vehicles for intercellular influence across the entire tumor landscape (4, 23, 47). In the vascular compartment, HNSCC-derived EVs have been shown to activate and aggregate platelets through tissue factor in a calcium-dependent manner, potentially facilitating hematogenous metastasis and immune cloaking (48). Strategies to disrupt EV-mediated signaling networks include pharmacologic inhibitors of vesicle secretion, antibodies targeting surface ligands, CRISPR-Cas9-based gene editing, and engineered EVs designed to deliver immunomodulatory or gene-silencing cargo, as illustrated in Figure 3.
Figure 3
3 Discussion
EVs have emerged as central regulators of tumor biology, playing multifaceted roles in driving oncogenesis, modulating immune responses, and promoting resistance to therapy. In HNSCC, a highly heterogeneous and aggressive malignancy, EVs enable dynamic intercellular communication that reinforces tumor progression and therapeutic failure. This review synthesizes current findings on the contributions of EVs to immune evasion, drug resistance, and metastasis in HNSCC. By elucidating these mechanisms, new avenues may emerge for leveraging EVs as diagnostic biomarkers and therapeutic targets in this challenging disease.
Our review found EVs in HNSCC to play a pivotal role in tumor progression by transferring oncogenic proteins, drug resistance factors, and immunosuppressive molecules, thereby promoting chemoresistance, immune evasion, and metastasis. Their ability to drive epithelial-mesenchymal transition, remodel the tumor microenvironment, and disseminate resistance traits across tumor sites highlighted their integrative function in maintaining malignant phenotypes.
However, despite the growing understanding of EV-mediated oncogenesis, literature revealed several challenges in studying and therapeutically targeting EVs. The heterogeneity of EV populations, the dynamic nature of their biogenesis, and the diversity in their molecular cargo present substantial obstacles in precisely defining their functional roles (12, 47). Additionally, the lack of standardized methods for EV isolation, characterization, and functional analysis continues to hinder the translation of laboratory findings into clinical applications (49, 50). Several recent advances are helping to overcome the technical challenges posed by EV heterogeneity and lack of standardized workflows. Updated protocols from the International Society for Extracellular Vesicles (MISEV) now provide widely adopted guidelines for EV nomenclature, isolation, and characterization, helping to reduce methodological variability across studies (51). On the technical front, bead-based multiplex assays and immunocapture platforms now allow for parallel profiling of distinct EV subpopulations from patient plasma or cell culture media (52). In addition, tools like tangential flow filtration (TFF), size-exclusion chromatography, and the exoRNeasy system have improved reproducibility and purity across isolation protocols (53). Single-EV profiling using nano-flow cytometry or super-resolution microscopy is also increasingly accessible, allowing researchers to resolve cargo heterogeneity within individual vesicles (54).
The immunomodulatory effects of EVs, particularly through PD-L1 delivery, further complicate the evolving landscape of immunotherapy in HNSCC. EV-mediated PD-L1 transfer enhances immune evasion by suppressing T-cell activity, creating an immunosuppressive microenvironment that favors tumor persistence and therapeutic resistance (7–9). The challenge of intercepting EV-driven immune escape necessitates novel strategies that restore immune surveillance and enhance the efficacy of immune checkpoint inhibitors.
Despite these challenges, targeting EV biogenesis, release, and uptake presents critical focus of ongoing translational research. Engineered EVs that selectively deliver anti-tumor agents, inhibitors of oncogenic pathways, or immune-modulating molecules offer a precision medicine approach to counteract EV-mediated disease progression, although therapeutic specificity remains complicated by EV heterogeneity (3, 4). Additionally, small-molecule inhibitors that block EV formation or disrupt their interactions with recipient cells could enhance the efficacy of existing treatments by mitigating drug resistance and limiting metastatic spread (5, 49). Heterogeneity presents a translational challenge because differences in vesicle origin, cargo, and surface markers complicate efforts to selectively target tumor-promoting subsets while preserving normal intercellular signaling. New technologies such as single-vesicle flow cytometry, high-resolution proteomics, and droplet-based microfluidics are enhancing the sensitivity and resolution of EV profiling, offering new avenues for dissecting EV subtypes and improving biomarker discovery (55–57). As research advances, the development of EV-targeted therapeutics and EV-based biomarkers has the potential to revolutionize cancer diagnostics and treatment paradigms (3, 5, 13).
This review underscores EVs as mediators of immune evasion, therapeutic resistance, and metastatic behavior in HNSCC. For clinicians, the translational potential lies in leveraging EVs as diagnostic biomarkers, such as for PD-L1 or drug-resistance markers and as novel therapeutic targets, including strategies that block EV secretion, uptake, or immunosuppressive cargo. Arginase-1 enrichment in plasma-derived EVs has been identified as a potential biomarker for metastatic disease in HNSCC patients, alongside other clinically investigated EV markers such as PD-L1, EGFR, and miR-21, offering minimally invasive tools for risk stratification and therapy response monitoring (58).
In addition to Arginase-1, several other EV-based applications are entering clinical workflows. PD-L1–expressing EVs have been proposed as predictive biomarkers to stratify patients for immune checkpoint inhibitor therapy, particularly in non-responders with low tumor cell PD-L1 expression but high EV-PD-L1 burden (59). Moreover, liquid biopsies leveraging EV cargo such as miR-21 and EGFR have shown promise in early detection and recurrence monitoring, with prospective trials exploring their integration into routine follow-up protocols (60). Therapeutically, engineered EVs are being developed to deliver targeted siRNAs, CRISPR-Cas9 systems, or immune ligands to tumor sites, enabling cell-type–specific modulation with minimal systemic toxicity (34). For example, miR-34a has shown potent anti-tumor effects in HNSCC xenograft models when delivered using chemically stabilized mimics, and its therapeutic delivery via engineered EVs is currently under investigation in other cancer types, supporting its potential for EV-based applications in HNSCC (61).
EVs from HNSCC are increasingly studied for liquid biopsy. For example, circulating exosomal PD‐L1 levels correlate with tumor stage and can predict relapse (62). Similarly, tumor‐derived exosomal EGFR and phospho‐EGFR fall during anti‐EGFR (cetuximab) therapy, suggesting EV‐EGFR can monitor therapeutic response (63). EV‐microRNAs also show promise: an 11‐miRNA signature in serum EVs robustly detected HPV+ oropharyngeal SCC (64). On the therapy side, EVs can be engineered as drug carriers. Engineered EVs have been loaded with siRNAs, cytokines or even gene‐editing systems (e.g., CRISPR/Cas9) to modulate tumors (65, 66). For instance, exosomes displaying immunostimulatory ligands or checkpoint inhibitors have been constructed to activate T cells (7, 67). Several clinical trials now involve EV platforms. For instance, a Phase I trial (NCT03608631) is testing MSC‐derived exosomes delivering KRAS‐G12D siRNA in pancreatic cancer (68). In fact, multiple EV‐based trials (most using MSC or dendritic‐cell EVs) are registered for solid tumors (69).
However, clinical translation and translation to HNSCC in particular faces key hurdles: the heterogeneity of EV populations, lack of standardization in isolation and profiling methods, and incomplete understanding of their biological roles all limit current applicability. Furthermore, selectively targeting tumor-promoting EVs without disrupting physiological intercellular communication remains a major challenge. For patients, the promise of EV-based interventions is substantial, offering hope for more personalized and effective therapies—especially in refractory or recurrent disease—but realization of these benefits will depend on robust clinical validation. Overall, future research must focus on refining EV detection technologies, validating EV-based biomarkers in large patient cohorts, and rigorously testing EV-targeted therapies in preclinical and clinical models.
4 Conclusion
By shaping the tumor microenvironment, promoting immune escape, and facilitating metastasis, EVs serve as key drivers of therapeutic resistance and disease persistence. Their biofluid stability, tumor-derived cargo, and immunomodulatory roles make EVs promising candidates for precision diagnostics and therapeutic targeting in HNSCC. However, clinical translation is limited by the heterogeneity of EV populations, lack of standardization in isolation and characterization methods, and incomplete understanding of their context-specific functions. Future work should focus on refining EV profiling techniques, developing selective targeting strategies, and validating clinical applications in well-designed studies. As our understanding deepens, EVs may ultimately offer a novel framework for precision diagnostics and therapy in HNSCC.
Statements
Author contributions
JD: Formal Analysis, Writing – original draft, Investigation. TN: Investigation, Methodology, Writing – original draft. CH: Visualization, Conceptualization, Writing – original draft. BM: Writing – review & editing, Investigation. BW: Writing – review & editing. FM: Writing – review & editing. GH: Writing – review & editing. MR: Writing – review & editing. MH: Writing – review & editing. JV: Writing – review & editing. AP: Writing – review & editing. SK: Conceptualization, Writing – review & editing, Supervision. LK: Supervision, Writing – review & editing, Conceptualization.
Funding
The author(s) declare that no financial support was received for the research, and/or publication of this article.
Conflict of interest
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The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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Glossary
- ABC
ATP-binding cassette
- ABCG2
ATP-binding cassette sub-family G member 2
- ALIX
Apoptosis-linked gene 2-interacting protein X
- BER
Base excision repair
- Bcl-2
B-cell lymphoma 2
- CAF
Cancer-associated fibroblast
- DAMP
Damage-associated molecular pattern
- DLS
Dynamic light scattering
- EGFR
Epidermal growth factor receptor
- ECM
Extracellular matrix
- ESCRT
Endosomal sorting complex required for transport
- EV
Extracellular vesicle
- HIF
Hypoxia-inducible factor
- HNSCC
Head and neck squamous cell carcinoma
- HSP
Heat shock protein
- IL-8
Interleukin-8
- ITGA6
Integrin alpha-6
- ITGB1
Integrin beta-1
- LGALS3BP
Galectin-3-binding protein
- lncRNA
Long non-coding RNA
- LAMP1
Lysosomal-associated membrane protein 1
- LAMP2
Lysosomal-associated membrane protein 2
- MAPK
Mitogen-activated protein kinase
- MMP
Matrix metalloproteinase
- MRP1
Multidrug resistance protein 1
- MVB
Multivesicular body
- mRNA
Messenger RNA
- NER
Nucleotide excision repair
- NTA
Nanoparticle tracking analysis
- PD-1
Programmed cell death protein 1
- PD-L1
Programmed death-ligand 1
- PDCD6IP
Programmed cell death 6-interacting protein
- PI3K/AKT
Phosphoinositide 3-kinase/Protein kinase B
- PS
Phosphatidylserine
- PTEN
Phosphatase and tensin homolog
- SEC
Size-exclusion chromatography
- SSB
Single-strand break
- siRNA
Small interfering RNA
- TAA
Tumor-associated antigens
- TGF-β
Transforming growth factor beta
- TIL
Tumor-infiltrating lymphocyte
- TME
Tumor microenvironment
- TNM
Tumor-node-metastasis classification system
- TSG101
Tumor susceptibility gene 101
- VEGF
Vascular endothelial growth factor
- VIM
Vimentin
- XRCC1
X-ray repair cross-complementing protein 1.
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Summary
Keywords
extracellular vesicles, head and neck squamous cell carcinoma, immune evasion, therapy resistance, tumor microenvironment
Citation
Dean J, Niederegger T, Hoch CC, Maheta B, Wollenberg B, Mrosk F, Hundeshagen G, Richter M, Heiland M, Voss J, Panayi AC, Koerdt S and Knoedler L (2025) Extracellular vesicles in head and neck cancer: mediators of oncogenesis, immune evasion, and therapy resistance. Front. Immunol. 16:1642639. doi: 10.3389/fimmu.2025.1642639
Received
06 June 2025
Accepted
28 August 2025
Published
19 September 2025
Volume
16 - 2025
Edited by
Italia Falcone, Regina Elena National Cancer Institute (IRCCS), Italy
Reviewed by
Misba Majood, Johns Hopkins University, United States
Dr. Shilpi Gupta, Amity University Uttar Pradesh, India
Updates
Copyright
© 2025 Dean, Niederegger, Hoch, Maheta, Wollenberg, Mrosk, Hundeshagen, Richter, Heiland, Voss, Panayi, Koerdt and Knoedler.
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: Leonard Knoedler, leonard.knoedler@charite.de
†These authors have contributed equally to this work
Disclaimer
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