Targeting CTLA-4 in Cancer: Biological Insights with a Focus on Renal Cell Carcinoma

Abstract

Renal cell carcinoma (RCC) is a complex group of malignant tumors characterized by immunosuppression and high invasiveness. In the majority of patients with advanced renal cell carcinoma, treatment fails to achieve a complete cure post-treatment. Efforts are needed to develop new therapeutics to improve the outcome of renal cell carcinoma. The "immune checkpoint" of T cells has attracted much attention in tumor immunotherapy. It is widely accepted that suppressor T cell immune checkpoints promote tumor immune escape through negative immune regulatory signals (cytotoxic T lymphocyte associated antigen 4 [CTLA-4], programmed cell death 1 [PD-1], B7-H3, and B7-H4, among others). The current data suggest that the PD-1 and CTLA-4 receptors inhibit the T cell receptor and its proliferation. Blockade of the PD-I/PD-L1 and/or CTLA-4/CD 28 pathways has shown favorable tumor outcomes in clinical trials in advance-stage renal cancer. This article reviews the role of CTLA-4/CD 28 pathway in renal cell carcinoma. Here we discuss the basics of the CTLA-4 pathway from a physiological perspective and evaluate the results of clinical studies of CTLA-4 alone and in combination with PD-1/PD-L1 blockers to support future studies of combination immunotherapy.