Tumor-infiltrating CD39+CD8+ T cells determine poor prognosis and immune evasion in clear cell renal cell carcinoma patients

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2020-08, Vol.69 (8), p.1565-1576
• Main Authors: Qi, Yu, Xia, Yu, Lin, Zhiyuan, Qu, Yang, Qi, Yangyang, Chen, Yifan, Zhou, Quan, Zeng, Han, Wang, Jiajun, Chang, Yuan, Bai, Qi, Wang, Yiwei, Zhu, Yu, Xu, Le, Chen, Lingli, Kong, Yunyi, Zhang, Weijuan, Dai, Bo, Liu, Li, Guo, Jianming, Xu, Jiejie
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antitumor activity; Apyrase - antagonists & inhibitors; Apyrase - metabolism; Bioinformatics; Biomarkers, Tumor - analysis; Cancer Research; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - pathology; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Clear cell-type renal cell carcinoma; Female; Flow cytometry; Follow-Up Studies; Humans; Immune evasion; Immune Evasion - drug effects; Immune Evasion - immunology; Immunology; Kidney cancer; Kidney Neoplasms - drug therapy; Kidney Neoplasms - immunology; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - drug effects; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Macrophages; Male; Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original; Original Article; Patients; PD-1 protein; Peripheral blood; Prognosis; Protein-tyrosine kinase; Retrospective Studies; Survival Rate; Therapeutic applications; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology; Tumor necrosis factor-α; Young Adult; γ-Interferon
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-020-02563-2

Purpose Tumor microenvironment is important in the progression of clear cell renal cell carcinoma (ccRCC), and its prognostic value is still unclear. Recent reports demonstrated tumor-infiltrating CD39 + CD8 + T cells are abundant, but their function remains obscure. We aim to assess clinical value of CD39 + CD8 + T cells and seek a potential therapeutic target in ccRCC. Experimental design We immunohistochemically evaluated clinical value of CD39 + CD8 + T cells in a retrospective Zhongshan Hospital cohort of 243 ccRCC patients. Fresh tumor samples ( n  = 48), non-tumor tissues and peripheral blood for flow cytometry analyses were collected to analyze immune cell functions from Zhongshan Hospital. The survival benefit of tyrosine kinase inhibitors (TKIs) in this subpopulation was evaluated. Kaplan–Meier analysis and COX regression model were applied for survival analyses. Bioinformatics analysis performed in TCGA KIRC cohort and the scRNA-seq cohort. Results We found that accumulation of CD39 + CD8 + T cells indicated poor prognosis ( p