Human leukocyte antigen-G isoforms HLA-G2/6, rather than HLA-G1/4/5, are associated with poorer survival in patients with epithelial ovarian cancer
Abstract
BackgroundThe novel immune checkpoint human leukocyte antigen-G (HLA-G) is a promising candidate target for solid cancer immunotherapy. However, knowledge gaps on the clinical relevance of diverse HLA-G isoforms remain.MethodsIn this study, with the successful generation of monoclonal antibodies (mAbs) against the HLA-G2/6 and HLA-G1/4/5 isoforms, the immunoreactivity scores (IRS) of both HLA-G2/6 and HLA-G1/4/5 expression (n = 304) were retrospectively analyzed using immunohistochemistry (IHC) in patients with epithelial ovarian cancer (EOC). The significance of the IRS status of HLA-G2/6 and HLA-G1/4/5 related to the clinical variables (n = 304) and prognosis (n = 251) of patients with EOC was evaluated.ResultsThe IRS of HLA-G2/6neg (n = 7), HLA-G2/6low (n = 105), and HLA-G2/6high (n = 192) and those of HLA-G1/4/5neg (n = 12), HLA-G1/4/5low (n = 48), and HLA-G1/4/5high (n = 244), respectively. Both HLA-G2/6high (p = 0.029) and HLA-G1/4/5high (p = 0.016) were the most frequently expressed in other EOC types, followed by the serous and mucinous subtypes. HLA-G2/6high was remarkably found in patients with advanced pN1 (p < 0.001), while HLA-G1/4/5high in patients with advanced pT3 (p = 0.024). The log-rank Mantel–Cox analysis showed that HLA-G2/6high was significantly associated with poorer overall survival (OS) (HLA-G2/6neg/low = 10.0 years vs. HLA-G2/6high = 6.25years; p = 0.036). Furthermore, patients with HLA-G2/6high had worse prognosis for those who are elder (>53 years, p = 0.049) and with the serous subtype (p = 0.028). However, HLA-G2/6 expression was not an independent prognostic risk factor for this EOC cohort.ConclusionsOur findings revealed, for the first time, that HLA-G2/6 rather than HLA-G1/4/5 isoform expression is associated with poorer survival in patients with EOC.
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BibTeX
@article{zhang2026human,
title = {{Human leukocyte antigen-G isoforms HLA-G2/6, rather than HLA-G1/4/5, are associated with poorer survival in patients with epithelial ovarian cancer}},
author = {Xia Zhang and Qiu-Yue Han and Bing-Ke Dai and Jian-Gang Zhang and Wei-Hua Yan and Aifen Lin},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1943243},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1943243},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Human leukocyte antigen-G isoforms HLA-G2/6, rather than HLA-G1/4/5, are associated with poorer survival in patients with epithelial ovarian cancer
AU - Xia Zhang
AU - Qiu-Yue Han
AU - Bing-Ke Dai
AU - Jian-Gang Zhang
AU - Wei-Hua Yan
AU - Aifen Lin
PY - 2026
DA - 2026/11/03
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1943243
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1943243
AB - BackgroundThe novel immune checkpoint human leukocyte antigen-G (HLA-G) is a promising candidate target for solid cancer immunotherapy. However, knowledge gaps on the clinical relevance of diverse HLA-G isoforms remain.MethodsIn this study, with the successful generation of monoclonal antibodies (mAbs) against the HLA-G2/6 and HLA-G1/4/5 isoforms, the immunoreactivity scores (IRS) of both HLA-G2/6 and HLA-G1/4/5 expression (n = 304) were retrospectively analyzed using immunohistochemistry (IHC) in patients with epithelial ovarian cancer (EOC). The significance of the IRS status of HLA-G2/6 and HLA-G1/4/5 related to the clinical variables (n = 304) and prognosis (n = 251) of patients with EOC was evaluated.ResultsThe IRS of HLA-G2/6neg (n = 7), HLA-G2/6low (n = 105), and HLA-G2/6high (n = 192) and those of HLA-G1/4/5neg (n = 12), HLA-G1/4/5low (n = 48), and HLA-G1/4/5high (n = 244), respectively. Both HLA-G2/6high (p = 0.029) and HLA-G1/4/5high (p = 0.016) were the most frequently expressed in other EOC types, followed by the serous and mucinous subtypes. HLA-G2/6high was remarkably found in patients with advanced pN1 (p < 0.001), while HLA-G1/4/5high in patients with advanced pT3 (p = 0.024). The log-rank Mantel–Cox analysis showed that HLA-G2/6high was significantly associated with poorer overall survival (OS) (HLA-G2/6neg/low = 10.0 years vs. HLA-G2/6high = 6.25years; p = 0.036). Furthermore, patients with HLA-G2/6high had worse prognosis for those who are elder (>53 years, p = 0.049) and with the serous subtype (p = 0.028). However, HLA-G2/6 expression was not an independent prognostic risk factor for this EOC cohort.ConclusionsOur findings revealed, for the first time, that HLA-G2/6 rather than HLA-G1/4/5 isoform expression is associated with poorer survival in patients with EOC.
SN - 1664-3224
ER -