Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 14, 2025

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy characterized by complex tumor microenvironment (TME) that plays pivotal role in initiation, progression, immune evasion. Recent advancements have highlighted the intricate interplay between infiltration patterns, checkpoint dysregulation, metabolic reprogramming driving HNSCC escape. Despite these insights, significant challenges remain, including incomplete understanding of specific evasion pathways lack personalized therapeutic strategies. To address gaps, this review introduces novel “Trinity” regulatory network HNSCC, encompassing: (1) reprogramming-mediated modulation, (2) stromal cell-driven dysfunction, (3) epigenetic remodeling fostering tolerance. This framework provides theoretical foundation for development multi-targeted combination therapies offers innovative strategies to overcome Additionally, systematically synthesizes current relationship escape, with focus on emerging immunotherapeutic approaches such as PD-1/PD-L1 inhibitors CAR-T therapy. Leveraging cutting-edge single-cell sequencing spatial transcriptomics, we elucidate spatiotemporal heterogeneity landscape propose new paradigm “lineage plasticity-driven adaptation.” These insights not only advance our biology but also pave way precision immunotherapies aimed at improving patient survival quality life. By integrating multidisciplinary perspectives, work underscores importance targeting TME achieve durable clinical responses immunotherapy resistance HNSCC.

Language: Английский