Construction of a novel prognostic signature based on the composition of tumor-infiltrating immune cells in clear cell renal cell carcinoma

Abstract

Emerging evidence has uncovered that tumor-infiltrating immune cells (TIICs) play significant roles in regulating the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC). However, the exact composition of TIICs and their prognostic values in ccRCC have not been well defined. A total of 534 ccRCC samples with survival information and TIIC data from The Cancer Genome Atlas (TCGA) dataset were included in our research. The ImmuCellAI tool was employed to estimate the abundance of 24 TIICs and further survival analysis explored the prognostic values of TIICs in ccRCC. In addition, the expression levels of immunosuppressive molecules (PDL1, PD1, LAG3, and CTLA4) in the high- and low-risk groups were explored. Various subtypes of TIICs had distinct infiltrating features and most TIICs exhibited dysregulated abundance between normal and tumor tissues. Moreover, specific kinds of TIICs had encouraging prognostic values in ccRCC. Further analysis constructed a 4-TIICs signature to evaluate the prognosis of ccRCC patients. Cox regression analyses confirmed the independent prognostic role of the signature in ccRCC. Moreover, immunosuppressive molecules, including PD1, LAG3, and CTLA4, were significantly upregulated in the high-risk group and predicted poor prognosis. However, PDL1 was not changed between high- and low-risk groups and could not predict poor prognosis. To sum up, our research explored the landscape of TIICs in ccRCC and established a novel 4-TIIC prognostic signature, which could effectively predict the prognosis for patients with ccRCC. Based on this signature, we also concluded that PDL1 may not predict prognosis in ccRCC.