Effector mechanisms of cd8+ hla‐dr+ t cells in breast cancer patients who respond to neoadjuvant chemotherapy

Abstract

Cytotoxic T lymphocyte (CTLs) activation is an independent predictor of response to neoadjuvant chemotherapy (NACT) in breast cancer (BC) patients. Here, we go deeper into the function of CD8+ HLA‐DR+T cells from NACT treated HER2 negative BC patients. Flow cytometry analysis revealed that CD8+ HLA‐DR+ T cell percentage was increased in NACT responder (R) compared to non‐responder (NR) patients. R patients with ER‐/PR‐ hormone receptors had the highest CD8+HLA‐DR+T cell frequencies, while no differences were found when patients were classified according to cancer stage or menopause status. Interestingly, the cytotoxicity and production of anti‐tumor cytokines were enhanced when CD8+ HLA‐DR+ T cells from healthy donors were cultured with plasma from R, but not from NR patients. The induced anti‐tumor profile of CD8+ HLA‐DR+ T cells was associated with plasmatic IL‐12 and IFN‐γ levels, increased cytokines in R patients. IL‐12 or IFN‐γ neutralization decreased cytotoxic activity and TNF‐α production by cultured CD8+ HLA‐DR+ T cells in R plasma presence. All these data suggest that an effective response to NACT in BC patients is associated with increased IL‐12 or IFN‐γ levels involved in the induction of cytotoxic and pro‐inflammatory mechanisms in CD8+ HLA‐DR+ T cells.