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Updated: Jul 16, 2025
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
TIGIT may Serve as a Potential Target for the Immunotherapy of Renal Cell Carcinoma
Xin Hong1, Chengfan Yu1, Jianlong Bi2
1Department of Urology, Peking University International Hospital, Beijing, 102206, China.
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.
Insights
TIGIT shows promise as an immunotherapy target for renal cell cancer (RCC). Blocking TIGIT and PD-1 inhibits RCC cell growth and promotes apoptosis, with TIGIT inhibitors being more effective.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Renal cell cancer (RCC) remains a significant challenge in oncology.
- Immune checkpoint inhibitors like PD-1 are established therapies, but novel targets are needed.
- TIGIT (T cell immunoreceptor with Ig and ITIM domains) is a potential immune checkpoint target.
Purpose of the Study:
- To investigate TIGIT as a potential immunotherapy target for RCC.
- To compare the efficacy of TIGIT inhibition with PD-1 inhibition in RCC.
- To explore the correlation between TIGIT and PD-1 expression in RCC.
Main Methods:
- Evaluation of TIGIT and PD-1 expression in RCC tissues and peripheral blood mononuclear cells (PBMC).
- Assessment of TIGIT and PD-1 expression correlation with other immune markers (PDCD1, BTLA, ICOS, FOXP3).
- Inhibition of TIGIT and PD-1 pathways to assess effects on RCC cell proliferation, apoptosis, and migration.
Main Results:
- TIGIT expression was higher than PD-1 in RCC tissues and PBMC.
- TIGIT expression positively correlated with PDCD1, BTLA, ICOS, and FOXP3.
- Inhibition of TIGIT and PD-1 significantly reduced RCC cell proliferation and migration while increasing apoptosis.
- TIGIT inhibition demonstrated greater efficacy than PD-1 inhibition.
Conclusions:
- TIGIT is a promising target for RCC immunotherapy.
- TIGIT inhibition effectively restores anti-tumor immune response in RCC.
- Combination therapy with TIGIT and PD-1 inhibitors may offer enhanced therapeutic benefits for RCC.
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