The prognostic impact of soluble and vesicular HLA-G and its relationship to circulating tumor cells in neoadjuvant treated breast cancer patients

Hum Immunol. 2016 Sep;77(9):791-9. doi: 10.1016/j.humimm.2016.01.002. Epub 2016 Jan 12.

Abstract

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-Gtot) and HLA-G levels in ExoQuick™ derived EV fractions (sHLA-GEV) by ELISA. The corresponding increments were specified as free sHLA-G (sHLA-Gfree). Total and free sHLA-G were significantly increased in NACT treated BC patients compared to healthy controls (n=16). High sHLA-Gfree levels were exclusively associated to estrogen receptor expression before NACT. Importantly, high sHLA-GEV levels before NACT were related to disease progression and the detection of stem cell-like circulating tumor cells, but high sHLA-Gfree 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.

Keywords: Breast cancer; Extracellular vesicles; Neoadjuvant chemotherapy; Prognostic impact; sHLA-G.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Proteins / metabolism*
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / drug therapy
  • Carcinoma, Ductal / diagnosis*
  • Carcinoma, Ductal / drug therapy
  • Cell-Derived Microparticles / metabolism*
  • Disease Progression
  • Female
  • HLA-G Antigens / metabolism*
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplastic Cells, Circulating / pathology*
  • Neoplastic Stem Cells / pathology*
  • Prognosis
  • Treatment Outcome
  • Tumor Escape
  • Young Adult

Substances

  • Blood Proteins
  • HLA-G Antigens