VISTA+/CD8+ status correlates with favorable prognosis in Epithelial ovarian cancer.

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.

• Authors: Aida Jlassi, Maroua Manai, Maram Morjen, Ghada Sahraoui, Monia Elasmi Allal, Ines ELBini-Dhouib, Lamia Naija, Lamia Charfi, Rim Rejaibi, Melika Ben Ahmed, Naziha Marrakchi, Najet Srairi-Abid, Amel Mezlini, Mohamed Manai, Karima Mrad, Raoudha Doghri
• Journal: PloS one (PLoS One) Vol. 18 Issue 3 Pg. e0278849 ( 2023) ISSN: 1932-6203 [Electronic] United States
• PMID: 36952478 (Publication Type: Journal Article)
• Copyright: Copyright: © 2023 Jlassi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Chemical References

• B7-H1 Antigen

Topics

• Humans
• Female
• Carcinoma, Ovarian Epithelial (metabolism)
• Leukocytes, Mononuclear (metabolism)
• Prognosis
• Ovarian Neoplasms (pathology)
• CD8-Positive T-Lymphocytes
• Lymphocytes, Tumor-Infiltrating
• B7-H1 Antigen (metabolism)
• Tumor Microenvironment