Abstract 6031: CD4+CD103+ tissue-resident memory T cells correlate with unfavorable prognosis in patients with head and neck cancer

Abstract T cell memory is an important mechanism for long-term protection against diverse pathogens such as cancers. Tissue-resident memory T cell (TRM) is a subset of memory T cells that stably resides in tissues and controls local immune homeostasis. In the present study, we investigated the immunological profile and clinical significance of TRM in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed RNA-sequencing data and clinical data obtained from The Cancer Genome Atlas (TCGA) database. In total, 520 cases, including 97 human papillomavirus (HPV)-positive HNSCCs and 423 HPV-negative HNSCCs, were analyzed. TRM-enriched tumors were identified based on the expression of both CD4/CD8A and ITGAE (CD103). TRM-enriched tumors tended to correlate with HPV-positive status and early T factor. Gene Set Enrichment Analysis revealed the enrichment of pathways relating to cytotoxic immune response in TRM-enriched tumors. Moreover, the expressions of immunostimulatory and immune checkpoint-related genes were elevated in TRM-enriched tumors. Notably, the enrichment of CD4+TRMs in tumors was an independent prognostic factor for shorter progression-free survivals (PFS). We also analyzed peripheral blood mononuclear cells obtained from 77 patients with HNSCC. The increased CD8+CD103+TRMs correlated with HPV-positive status and primary lesion of oropharynx. The proportion of CD4+CD103+TRMs negatively correlated with that of CD4+ naïve T cells, while that of CD8+CD103+TRMs negatively correlated with that of effector T cells. The proportion of CD4+CD103+TRMs positively correlated with Ki-67 expression in CD4+ T cells. Moreover, the elevated CD4+CD103+TRMs was an independent prognostic factor for shorter PFS. In conclusion, we highlighted the clinical and immunological significance of CD103+TRMs in both tumor tissues and peripheral blood of patients with HNSCC. Further characterization of TRMs could lead to the development of novel biomarkers for patients with HNSCC. Citation Format: Hideyuki Takahashi, Shota Ida, Hiroe Tada, Kazuaki Chikamatsu. CD4+CD103+ tissue-resident memory T cells correlate with unfavorable prognosis in patients with head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6031.