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Published on: January 12, 2020
VISTA+/CD8+ status correlates with favorable prognosis in Epithelial ovarian cancer
Aida Jlassi1,2, Maroua Manai1,3,4, Maram Morjen5
1Department of Biology, Mycology, Pathologies and Biomarkers Laboratory (LR16ES05), Faculty of Sciences of Tunis, University of Tunis El Manar, Ariana, Tunisia.
Abstract:
Immunotherapy by blocking immune checkpoint regulators has emerged as a new targeted therapy for some cancers. Among them V-domain Ig suppressor of Tcell activation (VISTA) which is identified as a novel checkpoint regulator in ovarian cancer. This study aimed to investigate the VISTA role in Epithelial ovarian cancer (EOC), and its relationship with tumor-infiltrating lymphocytes (TILs) markers and its prognostic value. The expression of VISTA, CD3, CD8, CD4, FOXP3, and CD56 was assessed in 168 EOC tissue microarrays (TMA) by immunohistochemistry (IHC). In addition, associations between VISTA, TILs, clinicopathological variables, and overall survival (OS) were analyzed. VISTA expression in IGRov1 cells, as well as in PBMC of EOC patient, was evaluated by western blot. VISTA expression was detected in 64,28% of tissues, among which 42.3% were positive for tumor cells (TCs), and 47,9% were positive for immune cells (ICs). In univariate analysis, VISTA expression was significantly associated with a high density of TILs:CD3+ (p = 0,001), CD4+ (p = 0,002) and CD8+ (p≤0,001), in ICs but not in TCs. In terms of OS, multivariate analysis showed a significant association between the high density of CD8+ TILs and VISTA positive staining in ICs (p = 0,044), but not in TCs (p = 0,108). Kaplan-Meier curves demonstrated no correlation between VISTA expression and prolonged OS in both ICs (p = 0,841) and TCs (p = 0,090). Classification of EOC tumor microenvironment based on VISTA and CD8+TILs expression, demonstrated four immune subtypes: VISTA+/CD8+, VISTA+/CD8-, VISTA-/CD8+ and VISTA-/CD8-. The dual positive VISTA+/CD8+ subtype was significantly associated with prolonged OS in both TCs and ICs (p = 0,012 and p≤0,01, respectively), whereas patients with VISTA+/CD8- had the worst OS. Our results showed that VISTA is highly expressed in the IGRov1 cell line and LT-CD8 from a patient with EOC. Our results highlighted the association of VISTA expression and CD8+ TILs in EOC, with prolonged OS in patients with VISTA+/CD8+ and proposed VISTA as a potential immunotherapeutic target in EOC.
Insights
V-domain Ig suppressor of T cell activation (VISTA) is expressed in ovarian cancer and associated with CD8+ T cells. The VISTA+/CD8+ subtype indicates prolonged overall survival, suggesting VISTA as a potential immunotherapy target.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Immunotherapy targeting immune checkpoint regulators is a promising cancer treatment.
- V-domain Ig suppressor of T cell activation (VISTA) is a novel checkpoint regulator identified in ovarian cancer.
Purpose of the Study:
- To investigate the role of VISTA in Epithelial ovarian cancer (EOC).
- To analyze the relationship between VISTA, tumor-infiltrating lymphocytes (TILs), and prognostic value in EOC.
Main Methods:
- Assessed VISTA, CD3, CD8, CD4, FOXP3, and CD56 expression in 168 EOC tissue microarrays (TMA) using immunohistochemistry (IHC).
- Evaluated VISTA expression in IGRov1 cells and peripheral blood mononuclear cells (PBMC) of EOC patients via western blot.
- Analyzed associations between VISTA, TILs, clinicopathological variables, and overall survival (OS).
Main Results:
- VISTA was detected in 64.28% of EOC tissues, with expression in tumor cells (42.3%) and immune cells (47.9%).
- VISTA expression in immune cells correlated significantly with high densities of CD3+, CD4+, and CD8+ TILs.
- The VISTA+/CD8+ immune subtype was significantly associated with prolonged OS, while VISTA+/CD8- correlated with the worst OS.
Conclusions:
- VISTA is highly expressed in EOC and associated with CD8+ TILs.
- The dual positive VISTA+/CD8+ subtype is linked to improved overall survival in EOC patients.
- VISTA represents a potential immunotherapeutic target for Epithelial ovarian cancer.
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