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

Shota Ida; Hideyuki Takahashi; Reika Kawabata-Iwakawa; Ikko Mito; Hiroe Tada; Kazuaki Chikamatsu

doi:10.1016/j.oraloncology.2021.105508

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

Oral Oncol. 2021 Nov:122:105508. doi: 10.1016/j.oraloncology.2021.105508. Epub 2021 Sep 8.

Authors

Shota Ida¹, Hideyuki Takahashi², Reika Kawabata-Iwakawa³, Ikko Mito¹, Hiroe Tada¹, Kazuaki Chikamatsu¹

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan.
² Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan. Electronic address: htakahas@gunma-u.ac.jp.
³ Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan.

PMID: 34507204
DOI: 10.1016/j.oraloncology.2021.105508

Abstract

Objectives: 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 (T_RMs) have been recognized as a subset capable of continuous immunosurveillance to afford long-term immunity. In the present study, we comprehensively profiled T_RM in patients with head and neck squamous cell carcinoma (HNSCC).

Materials and methods: 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 T_RM-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 T_RM-like cells in the peripheral circulation.

Results: TCGA analysis revealed that T_RM-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 + T_RM-like cells that highly express PD-1 and TIM-3 in the peripheral circulation of patients with HNSCC.

Conclusion: We highlighted the clinical and transcriptomic significance of T_RM in patients with HNSCC. Further characterization of T_RM could lead to the development of novel biomarkers, especially for immune checkpoint therapies.

Keywords: Head and neck squamous cell carcinoma; The Cancer Genome Atlas; Tissue-resident memory T cell; Tumor microenvironment; Tumor-infiltrating lymphocyte.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Head and Neck Neoplasms* / diagnosis
Head and Neck Neoplasms* / immunology
Humans
Lymphocytes, Tumor-Infiltrating
Memory T Cells*
Prognosis
Squamous Cell Carcinoma of Head and Neck* / diagnosis
Squamous Cell Carcinoma of Head and Neck* / immunology
Tumor Microenvironment*