Department of Urology, Peking University International Hospital, Beijing, 102206, China.
Department of Emergency, Peking University International Hospital, Beijing, 102206, China.
Adv Biol (Weinh). 2024 Jan;8(1):e2300050. doi: 10.1002/adbi.202300050. Epub 2023 Sep 10.
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.
本研究旨在探讨 TIGIT 是否可以作为 PD-1 的阳性对照,成为肾细胞癌(RCC)免疫治疗的有效靶点。评估 RCC 及外周血单个核细胞(PBMC)中 TIGIT 和 PD-1 的表达情况及其相关性,抑制 TIGIT 和 PD-1 的表达,评估其对细胞增殖、凋亡和迁移的影响。TIGIT 的表达与 PDCD1、BTLA、ICOS 和 FOXP3 的表达呈正相关(p<0.05)。PBMC、TIL、RCC 及相邻正常组织中 TIGIT 的表达均高于 PD-1 的表达。阻断 TIGIT 和 PD-1 信号通路可显著抑制 RCC 细胞的增殖、迁移和侵袭,促进其凋亡。TIGIT 抑制剂的作用比 PD-1 抑制剂更为明显。TIGIT 抑制剂主要通过调节差异基因的表达,实现免疫杀伤的重构,恢复对 RCC 的杀伤作用,其作用机制与 PD-1 抑制剂重叠。TIGIT 可能成为 RCC 免疫治疗的靶点,TIGIT 抑制剂与 PD-1 抑制剂联合治疗 RCC 具有理论基础。