HHLA2 predicts better survival and exhibits inhibited proliferation in epithelial ovarian cancer
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 immunohisto...
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doaj-edefff3e47554df8ba93361b0cb6cbde2021-05-09T11:21:19ZengBMCCancer Cell International1475-28672021-05-0121111410.1186/s12935-021-01930-yHHLA2 predicts better survival and exhibits inhibited proliferation in epithelial ovarian cancerGuocai Xu0Yuanyuan Shi1Xiaoting Ling2Dongyan Wang3Yunyun Liu4Huaiwu Lu5Yongpai Peng6Bingzhong Zhang7Department of Gynecologic Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Gynecologic Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Gynecologic Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Gynecologic Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Gynecologic Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Gynecologic Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Gynecologic Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Gynecologic Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityAbstract 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.https://doi.org/10.1186/s12935-021-01930-yHHLA2Immune checkpointPrognosisCD8+ tumour-infiltrating lymphocyteOvarian cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guocai Xu Yuanyuan Shi Xiaoting Ling Dongyan Wang Yunyun Liu Huaiwu Lu Yongpai Peng Bingzhong Zhang |
spellingShingle |
Guocai Xu Yuanyuan Shi Xiaoting Ling Dongyan Wang Yunyun Liu Huaiwu Lu Yongpai Peng Bingzhong Zhang HHLA2 predicts better survival and exhibits inhibited proliferation in epithelial ovarian cancer Cancer Cell International HHLA2 Immune checkpoint Prognosis CD8+ tumour-infiltrating lymphocyte Ovarian cancer |
author_facet |
Guocai Xu Yuanyuan Shi Xiaoting Ling Dongyan Wang Yunyun Liu Huaiwu Lu Yongpai Peng Bingzhong Zhang |
author_sort |
Guocai Xu |
title |
HHLA2 predicts better survival and exhibits inhibited proliferation in epithelial ovarian cancer |
title_short |
HHLA2 predicts better survival and exhibits inhibited proliferation in epithelial ovarian cancer |
title_full |
HHLA2 predicts better survival and exhibits inhibited proliferation in epithelial ovarian cancer |
title_fullStr |
HHLA2 predicts better survival and exhibits inhibited proliferation in epithelial ovarian cancer |
title_full_unstemmed |
HHLA2 predicts better survival and exhibits inhibited proliferation in epithelial ovarian cancer |
title_sort |
hhla2 predicts better survival and exhibits inhibited proliferation in epithelial ovarian cancer |
publisher |
BMC |
series |
Cancer Cell International |
issn |
1475-2867 |
publishDate |
2021-05-01 |
description |
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. |
topic |
HHLA2 Immune checkpoint Prognosis CD8+ tumour-infiltrating lymphocyte Ovarian cancer |
url |
https://doi.org/10.1186/s12935-021-01930-y |
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