VISTA immune checkpoint blunts radiotherapy-induced antitumor immune response
Summary: Radiotherapy (RT) is a key treatment for solid neoplasms like head and neck cancer (HNC), but it can also activate and recruit immunosuppressive myeloid cells, causing treatment failure. In this study, we examine the role of V-domain immunoglobulin suppressor of T cell activation (VISTA) on...
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| Language: | English |
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Elsevier
2025-07-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725006643 |
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| author | Dhanya K. Nambiar Sainiteesh Maddineni Jimpi Langthasa Hongbin Cao Vignesh Viswanathan Junyan Liu Md Tauhidul Islam Nishant Mehta Jessica Frank Alexander Real Tia Cheunkarndee Eyiwunmi Eghonghon Laseinde Bhushan Dharmadhikari Dipti Thakkar Jerome D. Boyd-Kirkup Andrey Finegersh Vasu Divi John B. Sunwoo John Aleman Xiao-Jing Wang Christina Kong Lei Xing Jennifer R. Cochran Quynh-Thu Le |
| author_facet | Dhanya K. Nambiar Sainiteesh Maddineni Jimpi Langthasa Hongbin Cao Vignesh Viswanathan Junyan Liu Md Tauhidul Islam Nishant Mehta Jessica Frank Alexander Real Tia Cheunkarndee Eyiwunmi Eghonghon Laseinde Bhushan Dharmadhikari Dipti Thakkar Jerome D. Boyd-Kirkup Andrey Finegersh Vasu Divi John B. Sunwoo John Aleman Xiao-Jing Wang Christina Kong Lei Xing Jennifer R. Cochran Quynh-Thu Le |
| author_sort | Dhanya K. Nambiar |
| collection | DOAJ |
| description | Summary: Radiotherapy (RT) is a key treatment for solid neoplasms like head and neck cancer (HNC), but it can also activate and recruit immunosuppressive myeloid cells, causing treatment failure. In this study, we examine the role of V-domain immunoglobulin suppressor of T cell activation (VISTA) on myeloid cells during RT. We discovered high VISTA expression on myeloid cells in the tumor microenvironment (TME) of both murine and human HNC, with RT increasing VISTA+ myeloid cells in the TME and circulation. Compared to VISTA+/+ mice, VISTA−/− mice showed improved tumor control with RT, with their macrophages and neutrophils exhibiting antitumorigenic properties on sc-RNA-seq analysis, especially with RT. Combining anti-VISTA antibodies (active or silent Fc) with RT (fractionated or ablative) significantly decreased tumor volume compared to either treatment alone in multiple preclinical models (HNC, breast cancer, and colorectal cancer), enhancing systemic antitumor immune response with augmented intra-tumoral T cell function through myeloid repolarization. Targeting VISTA could improve the efficacy of RT. |
| format | Article |
| id | doaj-art-3a19f3dce0404df6abd06110734032bc |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-3a19f3dce0404df6abd06110734032bc2025-08-20T03:27:01ZengElsevierCell Reports2211-12472025-07-0144711589310.1016/j.celrep.2025.115893VISTA immune checkpoint blunts radiotherapy-induced antitumor immune responseDhanya K. Nambiar0Sainiteesh Maddineni1Jimpi Langthasa2Hongbin Cao3Vignesh Viswanathan4Junyan Liu5Md Tauhidul Islam6Nishant Mehta7Jessica Frank8Alexander Real9Tia Cheunkarndee10Eyiwunmi Eghonghon Laseinde11Bhushan Dharmadhikari12Dipti Thakkar13Jerome D. Boyd-Kirkup14Andrey Finegersh15Vasu Divi16John B. Sunwoo17John Aleman18Xiao-Jing Wang19Christina Kong20Lei Xing21Jennifer R. Cochran22Quynh-Thu Le23Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA; Corresponding authorDepartment of Otolaryngology, Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USADepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USADepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USADepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USADepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USADepartment of Bioengineering, Stanford University Schools of Engineering and Medicine, Stanford, CA, USADepartment of Bioengineering, Stanford University Schools of Engineering and Medicine, Stanford, CA, USADepartment of Bioengineering, Stanford University Schools of Engineering and Medicine, Stanford, CA, USADepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USADepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USAHummingbird Bioscience, Singapore, SingaporeHummingbird Bioscience, Singapore, SingaporeHummingbird Bioscience, Singapore, SingaporeDepartment of Otolaryngology, Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Otolaryngology, Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Otolaryngology, Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USADepartment of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA; Department of Pathology and Laboratory Medicine, University of California, Davis, School of Medicine, Davis, CA, USA; VA Northern California Health Care System, Sacramento, CA, USADepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USADepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USADepartment of Bioengineering, Stanford University Schools of Engineering and Medicine, Stanford, CA, USADepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA; Corresponding authorSummary: Radiotherapy (RT) is a key treatment for solid neoplasms like head and neck cancer (HNC), but it can also activate and recruit immunosuppressive myeloid cells, causing treatment failure. In this study, we examine the role of V-domain immunoglobulin suppressor of T cell activation (VISTA) on myeloid cells during RT. We discovered high VISTA expression on myeloid cells in the tumor microenvironment (TME) of both murine and human HNC, with RT increasing VISTA+ myeloid cells in the TME and circulation. Compared to VISTA+/+ mice, VISTA−/− mice showed improved tumor control with RT, with their macrophages and neutrophils exhibiting antitumorigenic properties on sc-RNA-seq analysis, especially with RT. Combining anti-VISTA antibodies (active or silent Fc) with RT (fractionated or ablative) significantly decreased tumor volume compared to either treatment alone in multiple preclinical models (HNC, breast cancer, and colorectal cancer), enhancing systemic antitumor immune response with augmented intra-tumoral T cell function through myeloid repolarization. Targeting VISTA could improve the efficacy of RT.http://www.sciencedirect.com/science/article/pii/S2211124725006643CP: CancerCP: Immunology |
| spellingShingle | Dhanya K. Nambiar Sainiteesh Maddineni Jimpi Langthasa Hongbin Cao Vignesh Viswanathan Junyan Liu Md Tauhidul Islam Nishant Mehta Jessica Frank Alexander Real Tia Cheunkarndee Eyiwunmi Eghonghon Laseinde Bhushan Dharmadhikari Dipti Thakkar Jerome D. Boyd-Kirkup Andrey Finegersh Vasu Divi John B. Sunwoo John Aleman Xiao-Jing Wang Christina Kong Lei Xing Jennifer R. Cochran Quynh-Thu Le VISTA immune checkpoint blunts radiotherapy-induced antitumor immune response Cell Reports CP: Cancer CP: Immunology |
| title | VISTA immune checkpoint blunts radiotherapy-induced antitumor immune response |
| title_full | VISTA immune checkpoint blunts radiotherapy-induced antitumor immune response |
| title_fullStr | VISTA immune checkpoint blunts radiotherapy-induced antitumor immune response |
| title_full_unstemmed | VISTA immune checkpoint blunts radiotherapy-induced antitumor immune response |
| title_short | VISTA immune checkpoint blunts radiotherapy-induced antitumor immune response |
| title_sort | vista immune checkpoint blunts radiotherapy induced antitumor immune response |
| topic | CP: Cancer CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725006643 |
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