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VISTA immune-checkpoint blunts radiotherapy induced anti-tumor immune response

GSE295914 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2025/05/29 Platform GPL24247
Summary
Radiotherapy (RT) is a cornerstone treatment for cancers like head and neck cancer (HNC), but it can also unintentionally activate immune-suppressive myeloid cells, which may limit its effectiveness. This study explores the role of the immune checkpoint protein VISTA, which is found at high levels on myeloid cells in both mouse and human HNC tumors. RT further increases the number of VISTA-positive myeloid cells in the tumor and bloodstream. Mice lacking VISTA responded better to RT, with their immune cells–especially macrophages and neutrophils–shifting toward anti-tumor behavior, as revealed by single-cell RNA sequencing. Importantly, combining RT with anti-VISTA antibodies significantly shrank tumors in several cancer models (HNC, breast, colorectal), more so than either treatment alone. This combination also boosted the overall immune response, improving T cell activity through reprogramming of myeloid cells. These findings suggest that blocking VISTA could make RT more effective by counteracting immune suppression in the tumor environment.
Published in
VISTA immune checkpoint blunts radiotherapy-induced antitumor immune response
Nambiar DK, Maddineni S, Langthasa J et al. · Cell reports 2025 · PMID 40580480 · doi:10.1016/j.celrep.2025.115893
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Also filed as BioProject PRJNA1256782 and SRA study SRP582110. Searching any of these in the dataset finder brings you back here.

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