Human leukocyte antigen-G isoform HLA-G2/6, but not HLA-G1/4/5, is an independent indicator of poor survival in patients with colorectal cancer

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Detalles Bibliográficos
Publicado en:	Frontiers in Immunology vol. 16 (Oct 2025), p. 1672144-1672158
Autor principal:	Zhang, Xia
Otros Autores:	Qiu-Yue, Han, Zhang, Jian-Gang, Jiao, Lin, Wei-Hua, Yan, Lin, Aifen
Publicado:	Frontiers Media SA
Materias:	United States > US Shanghai China China Zhejiang China Monoclonal antibodies Metastasis Precision medicine Immunotherapy Cancer therapies Leukocytes Isoforms Ethics Peptides Colorectal cancer Colon cancer Clinical significance Cancer immunotherapy Laboratory animals Patients Tissue typing Medical prognosis Cloning Histocompatibility antigen HLA Immune response Immunohistochemistry Hospitals Committees Colorectal carcinoma Antigens
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Descripción
Resumen:	BackgroundHuman leukocyte antigen (HLA)-G has multiple isoforms with unique molecular structures and receptor-binding specificities. Different HLA-G isoform(s) may have distinct clinical relevance. Because of the lack of isoform-specific monoclonal antibodies (mAbs), the clinical significance of HLA-G isoforms (HLA-G1 to HLA-G7), except HLA-G1 and HLA-G5, remains largely unknown.MethodsIn this study, mAbs against HLA-G2/6 and HLA-G1/4/5 isoforms were generated and characterized. Expression of HLA-G2/6 and HLA-G1/4/5 isoforms was analyzed by immunohistochemistry, and clinical significance was evaluated retrospectively in 345 patients with colorectal cancer (CRC).ResultsThe expression rate of HLA-G2/6 (90/345, 26.1%) was significantly lower than that of HLA-G1/4/5 (275/345, 79.7%; p < 0.001). Patients with HLA-G2/6 expression had significantly poorer overall survival (OS) (median OS: 6.3 years [95% CI: 4.1–8.5] vs . 10.0 years [95% CI: 7.6–12.4]; p = 0.008). Multivariate Cox proportional-hazard model results indicated that HLA-G2/6 was an independent prognostic factor for CRC (hazard ratio [HR] = 1.530, 95% CI: 1.125–2.081; p = 0.007). Moreover, HLA-G2/6 expression showed stratified prognostic significance among several CRC patient subgroups, specifically in female patients (p = 0.003), younger patients (<66 years p < 0.001), patients with colon cancer ( p = 0.045), those at stage pT3 ( p = 0.008), pN1 ( p = 0.020), p M0 ( p = 0.009), and AJCC stage III ( p = 0.005). However, no statistical significance was found between HLA-G1/4/5 isoform expression and patient prognosis in CRC.ConclusionsThis is the first study to generate mAbs for the HLA-G2/6 and HLA-G1/4/5 isoforms. Our findings reveal that HLA-G2/6—but not HLA-G1/4/5—expression is an independent prognostic indicator for patients with CRC. In the context of precision medicine, our study also suggests that HLA-G isoform typing may be necessary for HLA-G-targeted cancer immunotherapy.
ISSN:	1664-3224
DOI:	10.3389/fimmu.2025.1672144
Fuente:	Health & Medical Collection