CTLA4 had a profound impact in the landscape of tumor-infiltrating lymphocytes with a high prognosis value in ccRCC

Abstract

Background Cytotoxic T-lymphocyte associated protein 4 (CTLA4) inhibitors have been shown to significantly prolong the overall survival (OS) in a wide range of cancers, however, its application is limited due to the therapy response and the prognostic value of CTLA4 in Clear cell renal cell carcinoma (ccRCC), which is the most common and fatal histological subtype in renal cell carcinoma, have not been investigated in detail. Methods In this study, we comprehensively and systematically studied the prognostic value of CTLA4 in ccRCC and its impact on the landscape of tumor-infiltrating lymphocytes (TILs) infiltration and genetic mutation through in vitro experiment and data mining. Results Our results showed that the CTLA4 was up-regulated in both ccRCC tissues and cell lines, and closely related to the disease progression as well as a poor prognosis. Deeper researches demonstrated that CTLA4 regulated the T cell activation and significantly linked to TIL-abundant tumor microenvironment (TME), but companies with an immunosuppressed phenotype, and CTLA4 was associated with more frequent BRCA-associated protein 1 (BAP1) mutation. Furthermore, given the current concerns caused by combined immunotherapy, we also found that CTLA4 was markedly correlated with multiple immune checkpoints, which suggested that ccRCC patients with high expressed CTLA4 may benefit more from immune checkpoint blockades (ICBs) combined therapy.Conclusion CTLA4 had a profound impact on the landscape of TILs and genetic mutation, as well as can be used as the biomarker with high prognosis value.