---
title: "VISTA promotes tumour-intrinsic proliferation in mesothelioma cells"
id: "british-journal-of-cancer-0-vista-drives-tumour-intrinsic-proliferation-in-mesothelioma-cells"
canonical_url: "https://medichelpline.com/clinical-feed/british-journal-of-cancer-0-vista-drives-tumour-intrinsic-proliferation-in-mesothelioma-cells"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "British Journal of Cancer"
source_url: "https://www.nature.com/articles/s41416-026-03639-z"
published_at: "2026-09-28T12:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# VISTA promotes tumour-intrinsic proliferation in mesothelioma cells
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/british-journal-of-cancer-0-vista-drives-tumour-intrinsic-proliferation-in-mesothelioma-cells
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** British Journal of Cancer
- **Source URL:** [Original Journal Publication](https://www.nature.com/articles/s41416-026-03639-z)
- **Published At:** 2026-09-28T12:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The study investigates the role of the immune checkpoint molecule **VISTA** (V-domain Ig suppressor of T cell activation) in mesothelioma cells, focusing on tumour-intrinsic effects rather than immune modulation. - Analysis of The Cancer Genome Atlas (TCGA) mesothelioma cohort showed high expression of **VISTA** and B7-H3 in mesothelioma; expression patterns correlated with genes characteristic of epithelioid (VISTA) and sarcomatoid (B7-H3) subtypes. - Functional experiments used mesothelioma cell lines and a mouse xenograft model to test effects of VISTA overexpression and knockdown on cell proliferation and tumour growth. - Overexpression of VISTA enhanced proliferation of mesothelioma cell lines in vitro; VISTA knockdown markedly suppressed tumour cell growth both in vitro and in vivo in xenografts. - Immunoprecipitation–mass spectrometry (IP–MS) identified VISTA-associated proteins, including cell adhesion molecules and intracellular signalling proteins such as receptor-interacting serine/threonine-protein kinase 1 (**RIPK1**). - RNA sequencing following manipulation of VISTA expression revealed enrichment of **TNF signalling** pathways and transcriptional changes consistent with altered proliferation-related programmes. - Functional analyses showed enhanced phosphorylation of **AKT** (protein kinase B) associated with VISTA expression, implicating AKT-dependent signalling in VISTA-driven proliferation. - The authors conclude that **VISTA** drives mesothelioma cell proliferation through tumour-intrinsic signalling independent of immune effects, and propose VISTA as a potential subtype-specific therapeutic target for mesothelioma. - Data generated in the study are deposited: RNA-seq in NCBI SRA (accession PRJNA1418830) and IP–MS in jPOST/ProteomeXchange (JPST004202); additional materials available from the corresponding author on request.
## Clinical Analysis & Structured Key Points
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[articles](https://www.nature.com/bjc/articles?type=article) 4. article * Article * Published: 28 September 2026 Cellular and Molecular Biology # VISTA drives tumour-intrinsic proliferation in mesothelioma cells * [Lisa Kondo-Ida](https://www.nature.com/articles/s41416-026-03639-z#auth-Lisa-Kondo_Ida-Aff1)[1](https://www.nature.com/articles/s41416-026-03639-z#Aff1), * [Tatsuhiro Sato](https://www.nature.com/articles/s41416-026-03639-z#auth-Tatsuhiro-Sato-Aff1) [ORCID: orcid.org/0000-0002-0689-1794](https://orcid.org/0000-0002-0689-1794)[1](https://www.nature.com/articles/s41416-026-03639-z#Aff1), * [Emi Mishiro-Sato](https://www.nature.com/articles/s41416-026-03639-z#auth-Emi-Mishiro_Sato-Aff2) [ORCID: orcid.org/0000-0001-5528-4440](https://orcid.org/0000-0001-5528-4440)[2](https://www.nature.com/articles/s41416-026-03639-z#Aff2), * [Satomi Mukai](https://www.nature.com/articles/s41416-026-03639-z#auth-Satomi-Mukai-Aff1) [ORCID: orcid.org/0009-0006-7988-6634](https://orcid.org/0009-0006-7988-6634)[1](https://www.nature.com/articles/s41416-026-03639-z#Aff1) & * … * [Yoshitaka Sekido](https://www.nature.com/articles/s41416-026-03639-z#auth-Yoshitaka-Sekido-Aff1-Aff3) [ORCID: orcid.org/0000-0002-2428-3848](https://orcid.org/0000-0002-2428-3848)[1](https://www.nature.com/articles/s41416-026-03639-z#Aff1),[3](https://www.nature.com/articles/s41416-026-03639-z#Aff3) Show authors [_British Journal of Cancer_](https://www.nature.com/bjc) (2026) [Cite this article](https://www.nature.com/articles/s41416-026-03639-z#citeas) [ Save article ](https://www.nature.com/articles/s41416-026-03639-z/save-research?_csrf=zlb-5OTIkK1FSEzH-olQQrTdOYRsObCj) [ View saved research ](https://www.nature.com/saved-research) ## Abstract ### Background Mesothelioma is a therapeutic challenge because current therapies have limited efficacy. In this study, we investigated the role of the immune checkpoint molecule V-domain Ig suppressor of T cell activation (VISTA) in mesothelioma cells. ### Methods The effect of VISTA expression on cell proliferation was analysed using mesothelioma cell lines and a mouse xenograft model. To investigate the underlying mechanisms, we performed immunoprecipitation–mass spectrometry and RNA-seq analysis to identify VISTA-associated proteins and downstream transcriptional changes. ### Results Analysis of The Cancer Genome Atlas (TCGA) dataset revealed that VISTA and B7-H3 were highly expressed in mesothelioma cells; their expression patterns were positively correlated with those of genes highly expressed in epithelioid and sarcomatoid cells, respectively. Functional studies revealed that VISTA overexpression enhanced proliferation of mesothelioma cell lines, whereas VISTA knockdown markedly suppressed tumour growth in vitro and in vivo. Proteomic profiling revealed interactions between VISTA, cell adhesion molecules and intracellular signalling proteins such as receptor-interacting serine/threonine-protein kinase 1 (RIPK1), whereas RNA sequencing revealed enrichment of TNF signalling, and functional analyses demonstrated enhanced AKT phosphorylation. ### Conclusions These findings indicate that VISTA promotes mesothelioma cell proliferation through tumour-intrinsic signalling independent of immune modulation. VISTA is a promising subtype-specific therapeutic target for mesothelioma. This is a preview of subscription content, [access via your institution](https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41416-026-03639-z) ## Access options [ Access through your institution ](https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41416-026-03639-z) Subscribe to this journal Receive 24 print issues and online access 251,40 € per year only 10,48 € per issue [Learn more](https://www.nature.com/bjc/subscribe) Buy this article * Purchase on SpringerLink * Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout ### Additional access options: * [Log in](https://idp.nature.com/auth/personal/springernature?client_id=grover&redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41416-026-03639-z) * [Learn about institutional subscriptions](https://www.springernature.com/gp/librarians/licensing/license-options) * [Read our FAQs](https://support.nature.com/en/support/home) * [Contact customer support](https://www.springernature.com/gp/contact) **Fig. 1: Analysis of V-domain Ig suppressor of T cell activation (VISTA) expression based on The Cancer Genome Atlas (TCGA) mesothelioma cohort analysis.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41416-026-03639-z/MediaObjects/41416_2026_3639_Fig1_HTML.png) **Fig. 2: VISTA knockdown suppresses mesothelioma cell proliferation in vitro.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41416-026-03639-z/MediaObjects/41416_2026_3639_Fig2_HTML.png) **Fig. 3: Identification and functional characterisation of VISTA-associated proteins by immunoprecipitation–mass spectrometry (IP–MS) analysis.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41416-026-03639-z/MediaObjects/41416_2026_3639_Fig3_HTML.png) **Fig. 4: VISTA alters gene expression profiles and modulates protein kinase B (AKT)-dependent signalling pathways.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41416-026-03639-z/MediaObjects/41416_2026_3639_Fig4_HTML.png) **Fig. 5: VISTA knockdown suppresses mesothelioma tumour growth in vivo.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41416-026-03639-z/MediaObjects/41416_2026_3639_Fig5_HTML.png) ### Explore related subjects Discover the latest articles and news in related subjects. * [Mesothelioma](https://www.nature.com/subjects/mesothelioma) * [Oncogenes](https://www.nature.com/subjects/oncogenes) ## Data availability The RNA-seq datasets generated during the current study have been deposited in the NCBI Sequence Read Archive (SRA) under the accession number PRJNA1418830. 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