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

Abstract

Blockading programmed death ligand 1 (PD-L1) shows promising results in patients with some cancers, but not in those with ovarian cancer. V-domain Ig suppressor of T cell activation (VISTA) is a recently discovered immune checkpoint protein that suppresses T cell activation. This study aimed to investigate the expression and clinical significance of VISTA in ovarian cancer as well as its relationship with PD-L1. VISTA and PD-L1 levels in 146 ovarian cancer samples were assessed using immunohistochemistry. We investigated the association between VISTA and other clinicopathological variables, including survival. The associations between the VISTA-encoding C10orf54 gene, other immune checkpoints, and survival were analyzed. VISTA was detected in 51.4% of all samples and 46.6% of PD-L1-negative samples; it was expressed in 28.8%, 35.6%, and 4.1% of tumor cells (TCs), immune cells (ICs), and endothelial cells, respectively. Furthermore, VISTA expression was associated with pathologic type and PD-L1 expression. Moreover, VISTA expression in TCs, but not in ICs, was associated with prolonged progression-free and overall survival in patients with high-grade serous ovarian cancer. The expression of C10orf54 mRNA was associated with prolonged overall survival and immune escape-modulating genes. These results showed that VISTA expression in ovarian tumor cells was associated with a favorable prognosis in patients with high-grade serous ovarian cancer; however, additional studies are required to better understand the expression and role of VISTA in ovarian cancer. Keywords Ovarian cancer • PD-L1 • VISTA • Immune checkpoints • Prognosis Abbreviations CTLA4 Cytotoxic T-lymphocyte-associated protein 4 FIGO International federation of gynecology and obstetrics HGSOC High-grade serous ovarian carcinoma IC Immune cell LAG3 Lymphocyte activation gene-3 TCGA The cancer genome atlas TC Tumor cell TIGIT T cell immunoreceptor with Ig and ITIM domains TIM-3 T cell immunoglobulin and mucin domain-3 TMA Tumor tissue microarray VISTA V-domain Ig suppressor of T cell activation Electronic supplementary material The online version of this article (

VISTA: an immune regulatory protein checking tumor and immune cells in cancer immunotherapy

“…Furthermore, VISTA expression was found associated with prolonged OS in ovarian cancer patients. Zong et al found that VISTA was expressed in TCs, ICs, and endothelial cells in ovarian cancer [41]. VISTA expression in ICs and all cells combined (TCs, ICs, and endothelial cells) was significantly more common in PD-L1-positive cells.…”

“…Liao et al found that VISTA expression increased with advanced disease stage and lymph node metastasis (LNM), indicating that VISTA expression is involved in the progression of ovarian cancer [40]. Zong et al concluded that VISTA expression in ovarian tumor cells was associated with a favorable prognosis in patients with high-grade serous ovarian cancer, and also closely related to the pathological type and PD-L1 expression [41]. In addition, VISTA mRNA expression was positively correlated with immune escapemodulating genes.…”

Prognostic significance and therapeutic potential of the immune checkpoint VISTA in pancreatic cancer

“…VISTA is mainly expressed in tumor-infiltrating immune cells (ICs) within the TME. However, in recent studies, VISTA was also detected in membranes of tumor cells (TCs), such as gastric, ovarian, and lung cancers (Boger et al 2017 ; Mulati et al 2019 ; Villarroel-Espindola et al 2018 ; Zong et al 2020b ). VISTA expresses on T cells as a part of an inhibitory immune checkpoint that suppresses T cell activation, proliferation, and cytokine production (ElTanbouly et al 2020 ; Flies et al 2011 ; Lines et al 2014 ).…”

<p>Emerging Targets of Immunotherapy in Gynecologic Cancer</p>

“…Likewise, in a study by Liao et al, the authors analyzed 65 ovarian cancer specimens and concluded that high VISTA expression on tumor or immune cells is significantly associated with advanced tumor stage and the presence of lymph node metastasis. 44 In contrast, Zong et al 45 assessed 146 ovarian cancer samples and found that 51.4% of the samples was exhibited VISTA expression and that VISTA was expressed in 28.8%, 35.6%, and 4.1% of tumor cells, immune cells, and endothelial cells, respectively. Notably, VISTA expression in tumor cells is associated with prolonged overall survival.…”