Response Gene to Complement 32 is associated with poor patient survival and an inflamed tumor-immune microenvironment in clear cell renal cell carcinoma

Abstract

It has been well established that tumor-infiltrating lymphocytes (TILs) play a critical role in the pathogenesis and progression of clear cell renal cell carcinoma (ccRCC). However, the mechanism on the interactions between TILs and tumor cells in the tumor-immune microenvironment remains unclear. In the present study, the expression of Response Gene to Complement 32 (RGC-32) was evaluated using immunohistochemistry. We analyzed the associations of RGC-32 expression with patient characteristics and survival. We also assessed TILs and their subsets (CD3⁺, CD4⁺, CD8⁺ and PD-1⁺) in the tumor nest. The level of RGC-32 expression was positively correlated with ISUP grade and Ki67 expression and was an independent poor prognosis factor of patients with ccRCC. RGC-32 expression was negatively correlated with the infiltration of TIL and CD3⁺T cells, but positively correlated with infiltration of PD-1⁺cells. In vitro studies showed that RGC-32 expression in renal cancer cells was downregulated by activated immune cells. Further investigation revealed that RGC-32 expression in renal cancer cells was inhibited by TNF-α and IL-1β secreted by activated immune cells. Collectively, these data indicate that RGC-32 could be a novel prognostic and druggable target related to the tumor-immune microenvironment in renal cancer.

Keywords: Inflammatory cytokines; RGC-32; Renal cancer; Tumor infiltrating lymphocytes; Tumor-immune microenvironment.