Journal Article

Dual targeting of TIGIT and VISTA in non-small-cell lung cancer immunotherapy

Mishra, Yachana, Qnais, Esam, Mishra, Vijay, Gammoh, Omar, Alqudah, Abdelrahim, El-Tanani, Mohamed, Aljabali, Alaa A A

2025

Overview

This study investigated the therapeutic impact of dual immune checkpoint inhibition targeting TIGIT and VISTA in non-small cell lung cancer (NSCLC). Current monotherapies have failed to produce consistent and durable responses owing to tumor heterogeneity and immune evasion. By evaluating the biological and immunomodulatory roles of TIGIT and VISTA, this study provides a rationale for their simultaneous blockade. Preclinical models have shown that this dual strategy not only revitalizes T-cell function but also alters the suppressive tumor microenvironment, leading to improved antitumor immunity in mice. Preliminary clinical data suggest potential survival benefits; however, the long-term outcomes and resistance dynamics remain uncertain. These findings suggest a paradigm shift toward precision-designed, multi-target immunotherapies. Future studies should integrate molecular profiling, adaptive clinical trial designs, and follow-up models to optimize patient selection and sustain therapeutic benefits. See also the graphical abstract(Fig. 1).

• Publisher: EXCLI Journal,IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund
• Subject: Antigens / Cancer immunotherapy / Cancer therapies / Cell death / Chemotherapy / Cytotoxicity / Dual immune checkpoint blockade / Immune checkpoint inhibitors / Immune system / Immunity (Disease) / Immunomodulation / Immunotherapy / Ligands / Lung cancer / Lymphocytes / Lymphocytes T / Non-small cell lung cancer / Non-small cell lung carcinoma / Patients / Pharmaceutical sciences / Pharmacy / Proteins / Radiation / Small cell lung carcinoma / T cell receptors / T-cell exhaustion / TIGIT / Tumor microenvironment / Tumor necrosis factor-TNF / Tumors / VISTA