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

Liju Zong,Yuncan Zhou,Yang Xiang,Ming Zhang,Jie Chen

doi:10.1007/s00262-019-02434-5

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.

Highlights

Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Ovarian cancer is the most lethal type of the gynecologic malignancy and accounts for the highest rate of gynecological cancer-related deaths worldwide
Among the 146 samples overall, V-domain Ig suppressor of T cell activation (VISTA) expression was detected in 51.4% (75 samples), while programmed death ligand 1 (PD-L1) was expressed in 8.9% (13 samples)
We discovered that VISTA is frequently expressed in PD-L1-negative ovarian cancer and that high VISTA expression is associated with a favorable prognosis in patients with high-grade serous ovarian carcinoma (HGSOC)

Summary

Introduction

295,414 patients were newly diagnosed with ovarian cancer in 2018, and 184,799 women died of this disease [1]. Surgery and adjuvant chemotherapy are effective for the majority of patients with ovarian cancer, more than 70% relapse, and their tumors eventually become chemotherapy resistant. In a study of 26 patients with PD-L1-expressing advanced ovarian cancer, the objective response rate to immunotherapy was 11.5% (only one patient achieved a complete response and two had partial responses) [3]. There is an urgent need to improve the outcomes of patients with ovarian cancer by better understanding the immune microenvironment of this tumor type and developing effective immunotherapeutic strategies [4]

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