Elevated sHLA-G plasma levels post chemotherapy combined with ILT-2 rs10416697C allele status of the sHLA-G-related receptor predict poorest disease outcome in early triple-negative breast cancer patients

Frontiers in Immunology

Immunology

Rainer Kimmig¹  Oliver Hoffmann¹  Ann-Kathrin Bittner¹  Sabine Kasimir-Bauer¹  Hana Rohn²  Sebastian Wormland³  Esther Schwich³  Julian Hölzenbein³  Vera Rebmann³  Peter A. Horn³  Sabine Schramm⁴ 

[1] Department of Gynecology and Obstetrics, University Hospital of Essen, Essen, Germany;National Center for Tumor Diseases (NCT), NCT West, Essen, Germany;Department of Infection Diseases, West German Centre of Infection Diseases, University Hospital of Essen, Essen, Germany;Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany;National Center for Tumor Diseases (NCT), NCT West, Essen, Germany;

关键词: triple-negative breast cancer;    early breast cancer (EBC);    biomarker;    ILT-2 rs10416697C allele;    sHLA-G;    CTC (circulation tumor cells);    HLA-G 3’ UTR;   

DOI  :  10.3389/fimmu.2023.1188030

 received in 2023-03-16, accepted in 2023-05-09,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionTriple negative breast cancer (TNBC) shows an aggressive growing and spreading behavior and has limited treatment options, often leading to inferior disease outcome. Therefore, surrogate markers are urgently needed to identify patients at high risk of recurrence and more importantly, to identify additional therapeutic targets enabling further treatment options. Based on the key role of the non-classical human leukocyte antigen G (HLA-G) and its related receptor immunoglobulin-like transcript receptor-2 (ILT-2) in immune evasion mechanisms of tumors, members of this ligand-receptor axis appear to be promising tool for both, defining risk groups and potential therapeutic targets.Materials and methodsTo follow this, sHLA-G levels before and after chemotherapy (CT), HLA-G 3’ UTR haplotypes, and allele variations rs10416697 at the distal gene promoter region of ILT-2 were defined in healthy female controls and early TNBC patients. The results obtained were associated with clinical status, presence of circulating tumor cell (CTC) subtypes, and disease outcome of patients in terms of progression-free or overall survival.ResultssHLA-G plasma levels were increased in TNBC patients post-CT compared to levels of patients pre-CT or controls. High post-CT sHLA-G levels were associated with the development of distant metastases, the presence of ERCC1 or PIK3CA-CTC subtypes post-CT, and poorer disease outcome in uni- or multivariate analysis. HLA-G 3’ UTR genotypes did not influence disease outcome but ILT-2 rs10416697C allele was associated with AURKA-positive CTC and with adverse disease outcome by uni- and multivariate analysis. The prognostic value of the combined risk factors (high sHLA-G levels post-CT and ILT-2 rs10416697C allele carrier status) was an even better independent indicator for disease outcome in TNBC than the lymph nodal status pre-CT. This combination allowed the identification of patients with high risk of early progression/death with positive nodal status pre-CT or with non-pathological complete therapy responseConclusionThe results of this study highlight for the first time that the combination of high levels of sHLA-G post-CT with ILT-2 rs10416697C allele receptor status is a promising tool for the risk assessment of TNBC patients and support the concept to use HLA-G/ILT-2 ligand-receptor axis as therapeutic targets.

【 授权许可】

Unknown   
Copyright © 2023 Hoffmann, Wormland, Bittner, Hölzenbein, Schwich, Schramm, Rohn, Horn, Kimmig, Kasimir-Bauer and Rebmann