Tissue-resident memory T cells correlate with the inflammatory tumor microenvironment and improved prognosis in head and neck squamous cell carcinoma
Tissue-resident memory T cells correlate with the inflammatory tumor microenvironment and improved prognosis in head and neck squamous cell carcinoma
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组织驻留记忆T细胞与头颈部鳞状细胞癌炎症微环境及预后改善相关
DOI：
10.1016/j.oraloncology.2021.105508
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发表时间：
2021-09-08
期刊：
影响因子：
4.8
通讯作者：
Chikamatsu, Kazuaki
中科院分区：
文献类型：
--
作者：
Ida, Shota;Takahashi, Hideyuki;Chikamatsu, Kazuaki
目的：肿瘤浸润性T细胞(TIL)是肿瘤微环境(TME)中参与肿瘤清除的主要细胞类型。在TIL中，组织驻留记忆T细胞(T(RM)S)被认为是一种能够持续免疫监视以提供长期免疫的亚群。在本研究中，我们全面分析了头颈部鳞状细胞癌(HNSCC)患者的T-RM。材料和方法：我们分析了来自癌症基因组图谱(TCGA)数据库的RNA测序(RNA-seq)数据。根据CD69和CD4/CD8A的基因表达，我们确定了T-RM富集者，并评价了其临床和生物学意义。此外，我们还分析了60例HNSCC患者的外周血单个核细胞(PBMC)，以评估外周血中T-RM样细胞的存在。结果：TCGA分析显示，T-RM样细胞丰富的肿瘤与早期T因子、人乳头状瘤病毒阳性状态、口咽病变比例、炎症途径上调、免疫刺激和免疫检查点分子基因上调以及总体预后相关。此外，我们还明确了HNSCC患者外周血中存在高表达PD-1和TIM-3的CD69+T-RM样细胞。结论：我们强调了T-RM在HNSCC患者中的临床和转录意义。T-RM的进一步表征可能导致新的生物标记物的开发，特别是用于免疫检查点治疗。
Objectives: Tumor-infiltrating T cell (TIL) is a major cell type involved in tumor eradication in the tumor microenvimnment (TME). Among TILs, tissue-resident memory T cells (T(RM)s) 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.