HHLA2 predicts better survival and exhibits inhibited proliferation in epithelial ovarian cancer

Guocai Xu,Yongpai Peng,Xiaoting Ling,Yuanyuan Shi,Dongyan Wang,Huaiwu Lu,Yunyun Liu,Bingzhong Zhang

doi:10.1186/s12935-021-01930-y

Guocai Xu, Yongpai Peng + Show 6 more

Open Access

https://doi.org/10.1186/s12935-021-01930-y

Copy DOI

Abstract

PurposeThe role of HHLA2, a new immune checkpoint ligand, is gradually being elucidated in various solid tumours. However, its role in ovarian cancer remains unclear; thus, its expression profile and clinical significance in ovarian cancer must be examined.MethodsWe performed immunohistochemistry to examine HHLA2 expression in 64 ovarian cancer tissues and 16 normal ovarian tissues. The relationships between HHLA2 expression and clinicopathological features, prognosis, and CD8+ tumour-infiltrating lymphocytes (TILs) in patients were analysed. Additionally, the Cancer Cell Line Encyclopedia database was used to analyse the correlation between HHLA2 expression and PD-L1 or B7x expression. Furthermore, the biological function of HHLA2 in ovarian cancer cells was initially explored.ResultsOnly 17.2% of ovarian cancer patients showed HHLA2 expression, which was significantly associated with the differentiation of ovarian cancer cells (p = 0.027), and well-differentiated tumours expressed higher levels of HHLA2. The density of CD8+ TIL was associated with increased HHLA2 expression (p = 0.017), and the CD8+ TIL count was higher in the HHLA2-positive group than that in the HHLA2-negative group (p = 0.023). Moreover, multivariate analysis identified HHLA2 expression as an independent prognostic factor that predicted improved survival (p = 0.049; HR = 0.156; 95% CI = 0.025–0.992). Additionally, we also found that overexpressing HHLA2 inhibited the proliferation of ovarian cancer cells.ConclusionHHLA2 is associated with tumour differentiation and high CD8+ TIL levels; and predicts improved survival in ovarian cancer. Along with previously reported findings that HHLA2 behaves as a co-stimulatory ligand, our study suggests that the loss of HHLA2 may contribute to the immunosuppressive microenvironment and progression of ovarian cancer.

Highlights

Ovarian cancer is a gynaecologic malignant disease, and more than 80% of patients with ovarian cancer present with advanced disease during diagnosis
Clinical and pathological features of patients and HHLA2 expression in ovarian cancer and normal ovarian tissue According to previous studies, HHLA2 protein is expressed in the villi of the placenta
HHLA2 was stained with anti-HHLA2 antibody, and HHLA2-positive staining was detected in a membranous and cytoplasmic pattern in ovarian cancer and normal ovarian tissue epithelium. a–d represented epithelial ovarian cancer tissue obtained from 64 patients with ovarian cancer who had undergo surgical resection between 2007 and 2011

Summary

Introduction

Ovarian cancer is a gynaecologic malignant disease, and more than 80% of patients with ovarian cancer present with advanced disease during diagnosis. The overall 5-year survival rate of ovarian cancer is < 30% [1]. According to the National Comprehensive Cancer Network (NCCN) guidelines, surgery and postoperative platinum-based chemotherapy are the primary treatments. Xu et al Cancer Cell Int (2021) 21:252 for ovarian cancer. Most patients will experience multiple recurrences, most of whom would die from platinum-resistant disease [2]. Identifying new treatment strategies remains an urgent need for ovarian cancer therapy. Anti-tumour immunotherapy has taken centre stage in mainstream oncology owing to the durable response rates in patients with multiple types of cancer [3]

Methods

Results

Discussion

Conclusion