Journal
HUMAN IMMUNOLOGY
Volume 77, Issue 9, Pages 791-799Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.humimm.2016.01.002
Keywords
Breast cancer; sHLA-G; Extracellular vesicles; Prognostic impact; Neoadjuvant chemotherapy
Categories
Funding
- IFORES, University of Duisburg-Essen [D/107-81080]
- Deutsche Krebshilfe [109816]
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The non-classical human leukocyte antigen G (HLA-G) molecule and its soluble forms exert multiple immune suppressive regulatory functions in malignancy and in stem cells contributing to immune escape mechanisms. HLA-G can be secreted as free soluble HLA-G molecules or via extracellular vesicles (EVs). Here we evaluated these soluble HLA-G forms as prognostic marker for prediction of the clinical outcome of neoadjuvant chemotherapy (NACT) treated breast cancer (BC) patients. Plasma samples of BC patients procured before (n = 142) and after (n = 154) NACT were quantified for total soluble HLA-G (sHLA-G(tot)) and HLA-G levels in ExoQuick (TM) derived EV fractions (sHLA-G(EV)) by ELISA. The corresponding increments were specified as free sHLA-G (sHLA-G(free)). Total and free sHLA-G were significantly increased in NACT treated BC patients compared to healthy controls (n = 16). High sHLA-G(free) levels were exclusively associated to estrogen receptor expression before NACT. Importantly, high sHLA-G(EV) levels before NACT were related to disease progression and the detection of stem cell-like circulating tumor cells, but high sHLA-G(tree) levels indicated an improved clinical outcome. Thus, this study demonstrates for the first time that the different sHLA-G subcomponents represent dissimilar qualitative prognostic impacts on the clinical outcome of NACT treated BC patients, whereas the total sHLA-G levels without separating into subcomponents are not related to clinical outcome. (C) 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
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