Immunotherapy by blockading the immune checkpoint regulators has emerged as new target for some cancer therapeutic. Recent studies have shown that patients who have developed resistance to immunotherapy combining a blockade of CTLA4 and PD1/PDL1 have a high expression of VISTA.VISTA (V-domain Ig-containing suppressor of T cell activation) was recently been investigated, and the evaluation of its inhibitory effect in combination with the anti-PDL1/PD1 and anti-CTLA4 has not been reported yet in ovarian cancer. Here, we evaluated the expression profile of VISTA, CTLA4, PDL1and PD1 its prognostic value in high-grade serous ovarian carcinoma (HGSOC) cohort.

Methods: The expression of checkpoints VISTA, CTLA4, PDL1, and PD1 was assessed in 135 HGSOC tissues microarrays by immunohistochemistry. Associations between the checkpoints, clinicopathological variables, and overall survival (OS) were analyzed. VISTA, CTLA4, PDL1, PD1 mRNA extracted from 429 patients with ovarian cancer in the Cancer Genome Atlas (TCGA) database was included as a validation cohort.

Results: CTLA4 was detectable in 87.3% of samples, VISTA in 64.7%, PD1 in 56.7%, and PDL1 in 48.1%. PDL1 was the only tested protein associated with an advanced stage (p=0.05). VISTA was associated with PDL1, PD1, and CTLA4 expressions (p=0.005, p=0.001, p=0.008, respectively), consistent with mRNA level analysis from the TCGA database. Univariate analyses showed only VISTA expression on tumor cells (TCs) was correlated with better OS (p=0.01). Multivariate analyses showed that VISTA expression and the coexpression VISTA+ /CTLA4+ /PD1+ 3 rd International Conference on Cancer and Breast Cancer Treatment November 03-04, 2025/ Dubai, UAE (p=0.01 and p=0.05, respectively) remain the independent predictor of a better OS. Kaplan-Meier analysis showed that only when VISTA expressed on TCs, VISTA+ /CTLA4+ /PDL1+ and VISTA+ /CTLA4+ /PD1+ were associated with a better OS (p=0.02 and p<0.001, respectively).

Conclusion: These correlations may refer to a new role of VISTA as a receptor in the TCs and not in the immune cells (ICs). Thus, targeting combination therapy blocking VISTA, CTLA4, and PD1 could be a novel and attractive strategy for HGSOC treatment, considering the ambivalent role of VISTA in the HGSOC tumor cells.

Aida JLASSI has completed her PHD at the age of 38 years from the faculty of Sciences at ELManar University, TUNISIA. She is a Post Doctor at Research Laboratory of Precision Medicine/Personalized Medicine and Oncology Investigation (LR21SP01) Salah Azaiz Institute, Tunisia. She has 2 publications in oncology/immunotherapy published in PLOSone and Frontiers in Oncology journals. She is dedicated to investigating new methods and strategies to improve cancer immunotherapy outcomes.