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

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.

Jlassi A ，Manai M ，Morjen M ，Sahraoui G ，Elasmi Allal M ，ELBini-Dhouib I ，Naija L ，Charfi L ，Rejaibi R ，Ben Ahmed M ，Marrakchi N ，Srairi-Abid N ，Mezlini A ，Manai M ，Mrad K ，Doghri R ... -  《PLoS One》

VISTA expression associated with CD8 confers a favorable immune microenvironment and better overall survival in hepatocellular carcinoma.

Zhang M ，Pang HJ ，Zhao W ，Li YF ，Yan LX ，Dong ZY ，He XF ... -  《BMC CANCER》

VISTA expression is associated with a favorable prognosis in patients with high-grade serous ovarian cancer.

Zong L ，Zhou Y ，Zhang M ，Chen J ，Xiang Y ... -  《-》

Prognostic value of tumor PD-L1 expression combined with CD8(+) tumor infiltrating lymphocytes in high grade serous ovarian cancer.

Expression of programmed cell death-ligand 1 (PD-L1) is known to be a mechanism whereby cancer can escape immune surveillance, but the relationship between tumor PD-L1 expression and tumor-infiltrating lymphocytes (TILs), and their association with clinical outcomes in patients with high grade serous ovarian cancer (HGSOC) remain ambiguous. We detected the expression of PD-L1 and CD3+, CD4+, CD8+ TILs in 107 patients with HGSOC by immunohistochemical analysis. Using a 5% threshold, 24.30% and 15.89% cases were found with positive expression of PD-L1 in the membrane of tumor cells and TILs respectively. Carcinoma PD-L1 expression mainly localized to the tumor invasive front and was associated with advanced FIGO stage (p=0.023) and abundant stromal CD8+ TILs infiltration (p=0.020). Tumors containing PD-L1+ TILs were more likely to have PD-L1 expression by the carcinoma cells (p<0.001). Univariate and multivariate analyses demonstrated that a higher number of intraepithelial CD3+ or CD8+ TILs was an independent prognostic factor for longer overall survival (OS), whereas tumor PD-L1 expression was a predictive factor for poorer OS only in univariate analysis. PD-L1 expression in TILs was not a prognostic factor in univariate analysis. The Kaplan-Meier curves of the four sub-groups and log-rank test showed that patients with negative tumor PD-L1 expression/higher numbers of intraepithelial CD8+ TILs had the longest median OS, while those with positive tumor PD-L1 expression/lower numbers of intraepithelial CD8+ TILs had the shortest median OS (p<0.001). Our results indicate that tumor PD-L1 expression in combination with intraepithelial CD8+ TILs infiltration has prognostic impact in patients with HGSOC. These biomarkers may be useful for the stratification of patients. Further evaluation of PD-1/PD-L1 as therapeutic targets for HGSOC is warranted.

Wang Q ，Lou W ，Di W ，Wu X ... -  《-》

VISTA/CTLA4/PD1 coexpression on tumor cells confers a favorable immune microenvironment and better prognosis in high-grade serous ovarian carcinoma.

Jlassi A ，Rejaibi R ，Manai M ，Sahraoui G ，Guerfali FZ ，Charfi L ，Mezlini A ，Manai M ，Mrad K ，Doghri R ... -  《Frontiers in Oncology》