Intra tumoral CD8-mediated type 1 anti-tumor responses and differentiated triple negative (TN) and HER-2 advanced breast cancer under neoadjuvant chemotherapy

Abstract

e22106 Background: To determine the predictive value of CD8 T cells tumor infiltrated lymphocytes (TIL) for treatment response in locally advanced breast cancer (LABC) primarily submitted to neoadjuvant chemotherapy. CD8 T cell-mediated immune responses fall into two distinct types based on effector cell-derived cytokine production. Type I CD8 T cells (Tc1) produce IFN-γ, whereas type 2 cells (Tc2) secrete IL-4, IL-5, IL-10, and GM-CSF. Methods: CD8 T cell, FoxP3 and stimulated anti-CD3 production of IFN-γ were quantitatively measured in the TIL sample from 22 consecutive patients with LABC using a FACS cell analyzing and enzyme immunoassay. Neoadjuvant treatment was given to all patients as Docetaxel 75 mg/m2 and Epirubicin 60 mg/m2 i.v. infusion, for one day, each 21/21 days. Results: Univariate analysis showed that CD8 T cell, FoxP3 and production of IFN-γ are more pronounced in Triple Negative (TN) tumor (39±4.1%, 44,15±11.2% and 17.66±9.18% respectivilly) than HER-2 tumor (30.2±3.4%; 31,7±2.62% and 9.69±6.07%) and this difference was not significantly changed by the neoadjuvant chemotherapy. Conclusions: The results suggest that mammary tumor growth and progression were dependent, in part, on effector cell-derived IFN-γ. Here we postulated that this condition was associated to response to neoadjuvante chemotherapy and was distinct expressed by different gene type of tumor breast. This suggested that CD8-mediated type 1 antitumor responses cannot only promote accumulation of distinct endogenous CD8 T cell subpopulations, but also facilitate and preferentially modulate their localization kinetics, persistence, states of activation/differentiation, and function within the primary tumor environment of tumor response/regression. The TN tumor was more chemo-sensitive and had high IFN-γ production. The action way could be done by CD44 high, FoxP3 and TGFβ1 and the activatioin of Treg in TIL that help in the tumor progression. The chemotherapy breaks this and facilitated the tumor regression. These studies offer insight into potential mechanisms for enhancing T cell-based immunotherapy in breast cancer. [Table: see text]