Mechanisms by which programmed cell death mediates immune evasion and antitumour immunity in oropharyngeal cancer.

Authors

Songxiao Yang, Ping Zhou

Published in

Frontiers in cell and developmental biology. Volume 14. Pages 1966827. Epub Oct 20, 2026.

Abstract

The development and treatment response of oropharyngeal squamous cell carcinoma (OPSCC) are jointly shaped by tumour cell-intrinsic features and the tumour immune microenvironment (TIME). Programmed cell death (PCD) determines tumour cell fate and modulates antitumour immunity by altering immunogenicity, the release of immunostimulatory signals and immune-cell function. Dysregulated PCD can enable tumour cells to evade immune recognition, establish an immunosuppressive state and alter the response to immunotherapy. Here, the roles of PCD in regulating immunity in oropharyngeal cancer (OPC) are reviewed, with emphasis on understanding at the molecular level how processes involved in apoptosis, ferroptosis, pyroptosis, and autophagy contribute to either immune evasion or antitumor immunity, with consideration given to emerging pathways involving necroptosis and cuproptosis. The immunological effects of cell death are thought to be context-dependent rather than predetermined by the mode of execution. Immunologically silent death can dampen these processes, reducing the immunogenicity of tumors, impairing antigen processing and presentation, and limiting T cell recognition; conversely, immunogenic cell death (ICD) can drive functional immunological responses through the release of damage-associated molecular patterns (DAMPs), improved antigen presentation, as well as adaptive immunity activation. Next, differences between human papillomavirus (HPV)-positive and HPV-negative OPSCC are discussed regarding PCD, TIME remodeling, immune checkpoint activation, and treatment resistance, as well as their translational relevance to precision immunotherapy, radiosensitization, and chemosensitization via subgroup-based combination therapy. Given the limited OPSCC-specific evidence for several emerging PCD pathways, related findings from head and neck squamous cell carcinoma (HNSCC) studies are discussed to provide mechanistic context. Together, these insights provide a framework for understanding immune evasion in OPC and for developing PCD-targeted therapeutic strategies.

PMID:
42978979
Bibliographic data and abstract were imported from PubMed on 04 Nov 2026.

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