CD8+ T Cell-Based Molecular Classification With Heterogeneous Immunogenomic Landscapes and Clinical Significance of Clear Cell Renal Cell Carcinoma

Frontiers in Immunology

Daojun Lv¹  Dongmei Jiang¹  Xiangkun Wu²  Xiaofan Lu²  Hongling Liu³  Li Liang⁵ 

[1] Guangdong Province Key Laboratory of Molecular Tumor Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China;;Department of Pathology &Department of Pathology, Nanfang Hospital and Basic Medical College, Southern Medical University, Guangzhou, China;Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;Department of Urology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China;

关键词: CD8+ T cells;    immunogenomic analysis;    immune checkpoint blockade therapy;    clear cell renal cell carcinoma;    unsupervised cluster analysis;   

DOI  :  10.3389/fimmu.2021.745945

来源: DOAJ

【 摘 要 】

The tumor microenvironment (TME) exerts a high impact on tumor biology and immunotherapy. The heterogeneous phenotypes and the clinical significance of CD8+ T cells in TME have not been fully elucidated. Here, a comprehensive immunogenomic analysis based on multi-omics data was performed to investigate the clinical significance and tumor heterogeneity between CD8+ T cell-related molecular clusters. We identified two distinct molecular clusters of ccRCC (C1 and C2) in TCGA and validated in E-MTAB-1980 cohorts. The C1 cluster was characterized by unfavorable prognosis, increased expression levels of CD8+ T cell exhaustion markers, high immune infiltration levels as well as more immune escape mechanisms. The C2 cluster was featured by favorable prognosis, elevated expression levels of CD8+ T cell effector markers, low load of copy number loss and low frequency of 9p21.3 deletion. Moreover, the effect of molecular classifications on Nivolumab therapeutic efficacy in the CheckMate 025 cohort was examined, and the C2 cluster exhibited a better prognosis. Taken together, we determine two CD8+ T cell-related molecular clusters in ccRCC, and provide new insights for evaluating the functions of CD8+ T cells. Our molecular classification is a potential strategy for prognostic prediction and immunotherapeutic guidance for ccRCC patients.

【 授权许可】

Unknown