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

Content Provider	Springer Nature : BioMed Central
Author	Xu, Guocai Shi, Yuanyuan Ling, Xiaoting Wang, Dongyan Liu, Yunyun Lu, Huaiwu Peng, Yongpai Zhang, Bingzhong
Abstract	Purpose The 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. Methods We 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. Results Only 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. Conclusion HHLA2 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.
Related Links	https://cancerci.biomedcentral.com/counter/pdf/10.1186/s12935-021-01930-y.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
ISSN	14752867
DOI	10.1186/s12935-021-01930-y
Journal	Cancer Cell International
Issue Number	1
Volume Number	21
Language	English
Publisher	BioMed Central
Publisher Date	2021-05-07
Access Restriction	Open
Subject Keyword	Cancer Research Cell Biology HHLA2 Immune checkpoint Prognosis CD8+ tumour-infiltrating lymphocyte Ovarian cancer
Content Type	Text
Resource Type	Article
Subject	Cancer Research Genetics Oncology
Journal Impact Factor	5.3/2023
5-Year Journal Impact Factor	5/2023

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