Editorial: The Tumor Microenvironment and Immunotherapy for Head and Neck Tumors

Yifan JiangLei Tao^*

• Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China

Head and neck tumors represent a highly heterogeneous group of malignancies, both biologically and anatomically, posing significant challenges to clinical research and therapeutic optimization. This heterogeneity is particularly relevant in the context of immunotherapy, where the diverse immune landscapes profoundly influence treatment outcomes. Central to this dynamic is the tumor microenvironment (TME), which plays a pivotal role in tumor progression, immune evasion, and response to immunotherapy (1).Despite the efficacy of immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 blockade, in a subset of head and neck squamous cell carcinoma (HNSCC) patients, therapeutic Intriguingly, the latter group displayed higher CD8+ T cell infiltration but pronounced functional exhaustion, marked by elevated PD-1 and LAG-3 expression. This paradox highlights the critical role of immune checkpoint activation and myeloid-derived suppressor cell (MDSC) enrichment in driving immune evasion, even in the context of robust T cell infiltration. Moreover, tertiary lymphoid structures (TLS) are emerging as critical components of anti-tumor immunity (4,5). Wu et al. developed a TLS scoring system, revealing that TLS presence correlated with PD-1+CXCL13+CD8+ T cell activity and improved immune responses in HNSCC patients. A case report by Jiang et al. examined the phenomenon of a "dissociated response" to immunotherapy, where certain tumor sites regress while others progress. This observation underscores the spatial heterogeneity of the TME and may influence treatment strategy in advanced head and neck cancer.Head and neck tumors frequently exhibit immune escape mechanisms that limit treatment efficacy. The identification of reliable biomarkers is crucial for predicting tumor progression Moving forward, fully realizing the potential of immunotherapy in this heterogeneous disease spectrum will require sustained multidisciplinary collaboration, well-designed clinical trials, and the integration of advanced technologies such as single-cell(9) and spatial omics (10).Ultimately, bridging the gap between mechanistic insights and clinical application will be crucial for improving outcomes in patients with head and neck tumors.