Identification of Immune-Related Subtypes and Characterization of Tumor Microenvironment Infiltration in Bladder Cancer

Frontiers in Cell and Developmental Biology

Jialin Meng¹  Li Xu³  Wenxuan Cheng³  Fangrong Yan³  Tong Jin³  Liwen Su³  Xinjia Ruan³  Yi Chen³  Xiaofan Lu³  Mengjia Huang³  Lin Liu³  Junkai Zhu³ 

[1] Anhui Province Key Laboratory of Genitourinary Diseases, Institute of Urology, Anhui Medical University, Hefei, China;Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China;State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China;

关键词: ICI;    immune subtype;    tumor microenvironment;    bladder cancer;    immunotherapy;   

DOI  :  10.3389/fcell.2021.723817

来源: DOAJ

【 摘 要 】

Tumors are closely related to the tumor microenvironment (TME). The complex interaction between tumor cells and the TME plays an indisputable role in tumor development. Tumor cells can affect the TME, promote tumor angiogenesis and induce immune tolerance by releasing cell signaling molecules. Immune cell infiltration (ICI) in the TME can affect the prognosis of patients with bladder cancer. However, the pattern of ICI of the TME in bladder cancer has not yet been elucidated. Herein, we identified three distinct ICI subtypes based on the TME immune infiltration pattern of 584 bladder cancer patients using the ESTIMATE and CIBERSORT algorithms. Then, we identified three gene clusters based on the differentially expressed genes (DEGs) between the three ICI subtypes. In addition, the ICI score was determined using single sample gene set enrichment analysis (ssGSEA). The results suggested that patients in the high ICI score subgroup had a favorable prognosis and higher expression of checkpoint-related and immune activity-related genes. The high ICI score subgroup was also linked to increased tumor mutation burden (TMB) and neoantigen burden. A cohort treated with anti-PD-L1 immunotherapy confirmed the therapeutic advantage and clinical benefit of patients with higher ICI scores. In the end, our study also shows that the ICI score represents an effective prognostic predictor for evaluating the response to immunotherapy. In conclusion, our study deepened the understanding of the TME, and it provides new ideas for improving patients’ response to immunotherapy and promoting individualized tumor immunotherapy in the future.

【 授权许可】

Unknown