Tissue-resident memory T cells correlate with the inflammatory tumor microenvironment and improved prognosis in head and neck squamous cell carcinoma

• Published in: Oral oncology 2021-11, Vol.122, p.105508-105508, Article 105508
• Main Authors: Ida, Shota, Takahashi, Hideyuki, Kawabata-Iwakawa, Reika, Mito, Ikko, Tada, Hiroe, Chikamatsu, Kazuaki
• Format: Article
• Language: English
• Subjects: Head and Neck Neoplasms - diagnosis; Head and Neck Neoplasms - immunology; Head and neck squamous cell carcinoma; Humans; Lymphocytes, Tumor-Infiltrating; Memory T Cells; Prognosis; Squamous Cell Carcinoma of Head and Neck - diagnosis; Squamous Cell Carcinoma of Head and Neck - immunology; The Cancer Genome Atlas; Tissue-resident memory T cell; Tumor Microenvironment; Tumor-infiltrating lymphocyte
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2021.105508

[Display omitted] •Tissue-resident memory T cell (TRM) enrichment correlated with clinical features.•TRM-enriched tumors exhibited upregulated inflammatory pathways.•TRM enrichment correlated with upregulated gene expression of checkpoint molecules.•Patients with head and neck cancer exhibit CD69 + TRM-like cells in peripheral blood. Tumor-infiltrating T cell (TIL) is a major cell type involved in tumor eradication in the tumor microenvironment (TME). Among TILs, tissue-resident memory T cells (TRMs) have been recognized as a subset capable of continuous immunosurveillance to afford long-term immunity. In the present study, we comprehensively profiled TRM in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed RNA-sequencing (RNA-seq) data obtained from The Cancer Genome Atlas (TCGA) database. Based on the gene expression of CD69 and CD4/CD8A, we identified TRM-enriched patients and evaluated their clinical and biological significance. In addition, we analyzed peripheral blood mononuclear cells (PBMCs) obtained from 60 patients with HNSCC to evaluate the presence of TRM-like cells in the peripheral circulation. TCGA analysis revealed that TRM-enriched tumors correlated with early T factor, human papillomavirus-positive status, the proportion of oropharynx lesion, upregulated inflammatory pathways, upregulation of immunostimulatory and immune checkpoint molecule genes, and favorable overall survival. Moreover, we clarified the presence of CD69 + TRM-like cells that highly express PD-1 and TIM-3 in the peripheral circulation of patients with HNSCC. We highlighted the clinical and transcriptomic significance of TRM in patients with HNSCC. Further characterization of TRM could lead to the development of novel biomarkers, especially for immune checkpoint therapies.