VISTA as an emerging immune checkpoint in cervical cancer: spatial immune regulation, myeloid–T Cell crosstalk, and therapeutic opportunities
- 1Key Laboratory of Pediatric and Female Malignant Tumors, Dalian Women and Children’s Medical Center (Group), The Affiliated Women and Children’s Hospital of Dalian University of Technology
- 2Department of Gynecology, General Hospital of Ningxia Medical University
Abstract
Immune checkpoint blockade has improved the treatment of cervical cancer, yet resistance remains a major clinical challenge. V-domain immunoglobulin suppressor of T-cell activation (VISTA; encoded by VSIR) is an emerging immune checkpoint expressed across myeloid cells, lymphocytes, and vascular endothelium. Its clinical significance appears context-dependent: some studies associate VISTA with unfavorable clinicopathological features, whereas others link abundant intratumoral VISTA-positive immune cells to improved survival. These findings highlight a critical distinction between checkpoint expression and functional immune suppression. This Mini Review synthesizes cervical cancer-specific pathology and mechanistic evidence from other tumor models, focusing on myeloid–T-cell crosstalk, T-cell quiescence, ligand-dependent regulation, and endothelial control of immune-cell trafficking. Interactions involving PSGL-1, VSIG-3, and LRIG1 suggest that VISTA activity varies across cellular and microenvironmental contexts, although their causal roles in cervical cancer remain to be established. Experimental studies support investigating VISTA blockade alongside established checkpoint inhibitors, but available clinical data have not demonstrated efficacy in cervical cancer. Future studies should integrate compartment-specific VISTA assessment, spatial immune profiling, and functional analyses of paired pretreatment and on-treatment specimens to identify VISTA-dependent immune states. Such an approach may provide a basis for biomarker-guided patient selection and rational development of VISTA-targeted immunotherapies.
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BibTeX
@article{li2026vista,
title = {{VISTA as an emerging immune checkpoint in cervical cancer: spatial immune regulation, myeloid–T Cell crosstalk, and therapeutic opportunities}},
author = {Wangshu Li and Wenjuan Wei and Di Wen and Aziz ur Rehman Aziz and Xiaohui Yu and Daqing Wang and Chunfang Ha},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.2015330},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.2015330/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - VISTA as an emerging immune checkpoint in cervical cancer: spatial immune regulation, myeloid–T Cell crosstalk, and therapeutic opportunities
AU - Wangshu Li
AU - Wenjuan Wei
AU - Di Wen
AU - Aziz ur Rehman Aziz
AU - Xiaohui Yu
AU - Daqing Wang
AU - Chunfang Ha
PY - 2026
DA - 2026/11/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.2015330
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.2015330/full
AB - Immune checkpoint blockade has improved the treatment of cervical cancer, yet resistance remains a major clinical challenge. V-domain immunoglobulin suppressor of T-cell activation (VISTA; encoded by VSIR) is an emerging immune checkpoint expressed across myeloid cells, lymphocytes, and vascular endothelium. Its clinical significance appears context-dependent: some studies associate VISTA with unfavorable clinicopathological features, whereas others link abundant intratumoral VISTA-positive immune cells to improved survival. These findings highlight a critical distinction between checkpoint expression and functional immune suppression. This Mini Review synthesizes cervical cancer-specific pathology and mechanistic evidence from other tumor models, focusing on myeloid–T-cell crosstalk, T-cell quiescence, ligand-dependent regulation, and endothelial control of immune-cell trafficking. Interactions involving PSGL-1, VSIG-3, and LRIG1 suggest that VISTA activity varies across cellular and microenvironmental contexts, although their causal roles in cervical cancer remain to be established. Experimental studies support investigating VISTA blockade alongside established checkpoint inhibitors, but available clinical data have not demonstrated efficacy in cervical cancer. Future studies should integrate compartment-specific VISTA assessment, spatial immune profiling, and functional analyses of paired pretreatment and on-treatment specimens to identify VISTA-dependent immune states. Such an approach may provide a basis for biomarker-guided patient selection and rational development of VISTA-targeted immunotherapies.
SN - 1664-3224
ER -