Work

Defining the tumor-infiltrating lymphocyte antigenic landscape in head and neck cancer 4114

Year: 2025

Type: article

Abstract: Description Adoptive cell transfer (ACT) with tumor-infiltrating lymphocytes (TIL) is a promising therapeutic approach for head and neck squamous cell carcinoma (HNSCC). We explored the potential to harness a polyclonal population of T cells via enriched specificity and reactivity toward tumor-derived antigens. Across 18 HNSCC samples, on average 119 somatic mutations and 89 25mers were discovered via whole exome and RNA sequencing and predicted to bind to each patient’s respective MHC. The first patient sample revealed a candidate neoantigen ‘hit’ resulting in activation of 45% of CD4+ TIL by OX40+/4-1BB+ induction. Neoantigen-reactive TIL secreted granzyme B, IFNg, and TNFa, in a dose-dependent manner, which was abrogated by HLA-DQ blockade. TCR sequencing revealed an oligoclonal T cell population. Pilot non-clinical ACT experiments in mice demonstrated TIL engraftment and tumor infiltration. Initial APC immunopeptidomics analysis found nine unique epitopes bound to MHC Class I and 17 peptides presented by MHC Class II following neoantigen pulse. Overall, expanded HNSCC TIL contain neoantigen-reactive effector T cells, and analysis of additional samples is ongoing. We aim to expand this investigation to better understand the landscape of T cell reactivity and the dynamic antigenic and cellular determinants involved in the anti-tumor immune response. Ultimately, we plan to determine the potential therapeutic benefit of an enriched antigen-reactive TIL-ACT product for HNSCC patients. Funding Sources This study was funded, at least in part, by Marshall Glenn Hoffman Oral Cancer Research Fund. Turnstone Biologics sponsored research agreement. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1835