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

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

PMC · DOI: 10.17179/excli2025-8735 · 2025-08-28

## TL;DR

This study explores combining two immune checkpoint inhibitors, TIGIT and VISTA, to improve treatment outcomes in non-small cell lung cancer.

## Contribution

The novelty lies in demonstrating the combined blockade of TIGIT and VISTA to enhance antitumor immunity in preclinical models.

## Key findings

- Dual inhibition of TIGIT and VISTA revitalizes T-cell function and reduces tumor suppression in mice.
- Preliminary clinical data suggest potential survival benefits from this dual-target approach.
- The study highlights the need for precision immunotherapies and adaptive clinical trial designs.

## Abstract

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).

## Linked entities

- **Proteins:** TIGIT (T cell immunoreceptor with Ig and ITIM domains), VSIR (V-set immunoregulatory receptor)
- **Diseases:** non-small cell lung cancer (MONDO:0005233)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** TIGIT (T cell immunoreceptor with Ig and ITIM domains) [NCBI Gene 201633] {aka VSIG9, VSTM3, WUCAM}, VSIR (V-set immunoregulatory receptor) [NCBI Gene 64115] {aka B7-H5, B7H5, C10orf54, DD1alpha, Dies1, GI24}
- **Diseases:** tumor (MESH:D009369), NSCLC (MESH:D002289)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12521746/full.md

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Source: https://tomesphere.com/paper/PMC12521746