Work

Macrophages suppress CD8 + T cell cytotoxic function in triple negative breast cancer via VISTA

Year: 2025

Type: article

Abstract: BACKGROUND: Immunotherapy targeting negative immune checkpoint regulators to enhance the anti-tumour immune response holds promise in the treatment of TNBC. V-domain Ig suppressor of T-cell activation (VISTA) is an immune checkpoint molecule, known to be upregulated and involved in modulating tumour immunity in TNBC. However, how VISTA affects immune response and its therapeutic potential in TNBC remains unclear. METHOD: Here, we examined VISTA expression and cellular distribution in TNBC patients' samples and pre-clinical TNBC mouse model. Functional assays were performed to assess the impact of VISTA blockade on macrophage phenotypes, CD8 + T cell infiltration and activation, and overall anti-tumour immune response. RESULTS: In this study we show that VISTA expression levels are increased in TNBC patients' samples and pre-clinical mouse models compared to non-involved breast tissue and VISTA is mainly expressed on tumour infiltrating macrophages and neutrophils. Blocking VISTA reverts macrophages immunosuppressive phenotypes, increases CD8 + T cell infiltration and activation, and enhances an anti-tumour immune response. Mechanistically, we show that neutralising VISTA on macrophages enhances their immune-stimulatory functions and inhibits the suppressive effect of macrophages on CD8 + T cells activation. CONCLUSION: These findings provide the rationale for the development of anti-VISTA targeting strategies in the treatment of TNBC.

Source: British Journal of Cancer

DOI: 10.1038/s41416-025-03013-5

Authors: Maidinaimu Abudula, Yuliana Astuti, Meirion Raymant, Vijay Sharma, Michael C. Schmid, Ainhoa Mielgo

Institutions: University of Liverpool, Liverpool University Hospitals NHS Foundation Trust

Language: English

Topic: Immune cells in cancer

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,190