T helper responses are maintained by basal-like breast cancer cells and confer to immune modulation via upregulation of PD-1 ligands


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Karasar P., ESENDAĞLI G.

BREAST CANCER RESEARCH AND TREATMENT, vol.145, no.3, pp.605-614, 2014 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 145 Issue: 3
  • Publication Date: 2014
  • Doi Number: 10.1007/s10549-014-2984-9
  • Journal Name: BREAST CANCER RESEARCH AND TREATMENT
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.605-614
  • Keywords: Basal-like breast cancer, T lymphocyte, Immune modulation, PD-1, PD-L1, PD-L2, TUMOR-INFILTRATING LYMPHOCYTES, SUBPOPULATIONS, EXPRESSION, EFFECTOR, SURVIVAL, ANTIBODY, CD4(+), SAFETY, B7-H1
  • Hacettepe University Affiliated: Yes

Abstract

A conspicuous T cell infiltration is frequently observed in triple-negative and/or basal-like breast cancers. Since the immunological course of breast cancer is explicitly directed by helper T cells, this study aims to determine the influence of basal-like breast cancer (BLBC) cells on CD4(+) T cell responses. Co-cultures were established with breast cancer cell lines and CD4(+) T cells under stimulatory conditions. Helper T cell activation, proliferation, cytokine secretion, and differentiation were assessed. Protein and mRNA expression of PD-1 ligands were determined on breast cancer cell lines. Blockade assays were performed in order to determine the functional assets of PD-1 ligation. In contrast to luminal breast cancer cells, BLBC cells allowed CD4(+) T cell activation, proliferation, and IFN-gamma secretion, but only to a certain extent. A substantial population of CD25(+)CD127(low/-) regulatory T (Treg) cells was also induced in BLBC co-cultures. In return, IFN-gamma stimulated the upregulation of PD-L1 (B7-H1) and/or PD-L2 (B7-DC) inhibitory molecules on the basal-like cells. In prolonged periods of co-culturing, blockade of PD-1 ligands on BLBC cell lines impaired Treg differentiation, restored IL-2 secretion, and increased CD8(+) T cell activation. In conclusion, T helper responses were maintained by BLBC cells. On the other hand, IFN-gamma secreted from Th1 and other immune cells upregulated the expression of PD-1 ligands on BLBC cells and modulated the immune reactions. Our results indicate the capacity of BLBCs to adapt to IFN-gamma-mediated anti-tumor immune responses and to evade immunity via upregulation of PD-1 ligands.