TIGIT may Serve as a Potential Target for the Immunotherapy of Renal Cell Carcinoma

Abstract

This study aims to explore whether TIGIT is an effective target for the immunotherapy of renal cell cancer (RCC) with PD‐1 as a positive control. The expression of TIGIT and PD‐1 in RCC and peripheral blood mononuclear cells (PBMC) and the correlation between TIGIT and PD‐1 are evaluated. The expression of TIGIT and PD‐1 is inhibited, and then the proliferation, apoptosis, and migration are assessed. TIGIT expression is positively related to the expression of PDCD1, BTLA, ICOS, and FOXP3 (p < 0.05). TIGIT expression in the PBMC, TIL, RCC, and adjacent normal tissues is higher than PD‐1 expression. Blocking the TIGIT and PD‐1 signaling pathways significantly inhibits the proliferation, migration, and invasion of RCC cells and promotes their apoptosis. These effects are more evident in TIGIT inhibitors than in PD‐1 inhibitors. TIGIT inhibitor mainly regulates the expression of differential genes to achieve the reconstruction of immune killing and restore the killing effect on the RCC, and its mechanism by which TIGIT functions overlap that of PD‐1 inhibitor. TIGIT may become a target for the immunotherapy of RCC, and there is a theoretical basis for the combination of TIGIT inhibitors and PD‐1 inhibitors for the treatment of RCC.

Emerging Immunotherapy Approaches for Advanced Clear Cell Renal Cell Carcinoma

“…The therapeutic landscape for RCC is continuously evolving, with substantial efforts focused on developing novel agents that target immune checkpoint proteins or signaling pathways. Key areas of investigation include immune checkpoints such as lymphocyte-activation gene 3 (LAG-3) [ 45 , 46 ], T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) [ 47 , 48 ], and T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domain (TIGIT) [ 49 , 50 ], alongside notable pathways including C-C motif chemokine ligand 2/C-C chemokine receptor type 2 (CCL2/CCR2) [ 51 , 52 ], Interleukin-1 (IL-1) [ 52 ], and Angiopoietin-2 (Ang2) [ 53 ]. The overarching objective is to enhance antitumor immune responses to improve patient outcomes.…”