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.
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.
We found that accumulation of CD39+CD8+ T cells indicated poor prognosis (p < 0.0001) and indicated therapeutic benefit of TKIs therapy (p = 0.015). CD39+CD8+ T cells showed decreased TNF-α and IFN-γ with elevated PD-1 and TIM-3 expression. Further analysis of tumor-infiltrating immune cell landscape in the ccRCC revealed the positive correlation between CD39+CD8+ T cells and Tregs (p = 0.037) and M2-polarized macrophages (p < 0.0001). Finally, inhibition of CD39 partially restores the anti-tumor function of CD8+ T cells.
High CD39+CD8+ T cells indicated poor prognosis in ccRCC, due to impaired anti-tumor function of CD39+CD8+ T cells and indicated therapeutic benefit of TKIs therapy.
Cancer immunology, immunotherapy : CII. 2020 Apr 18 [Epub ahead of print]
Yu Qi, Yu Xia, Zhiyuan Lin, Yang Qu, Yangyang Qi, Yifan Chen, Quan Zhou, Han Zeng, Jiajun Wang, Yuan Chang, Qi Bai, Yiwei Wang, Yu Zhu, Le Xu, Lingli Chen, Yunyi Kong, Weijuan Zhang, Bo Dai, Li Liu, Jianming Guo, Jiejie Xu
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China., Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China., Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China., Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China., Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China., Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China., Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. ., Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. ., Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. .