Tumor-infiltrating Treg, MDSC, and IDO expression associated with outcomes of neoadjuvant chemotherapy of breast cancer

Abstract

Background: Regulatory T cells(Tregs) and myeloid-derived suppressor cells(MDSCs) represent two immunosuppressive cell populations that are important in the establishment and maintenance of cancer immune tolerance. MDSCs can express IDO and promote immune tolerance via expansion of Treg cell.Method: We use needle biopsy breast cancer tissues prior to neoadjuvant chemotherapy(NCT) staining for CD33, Foxp3 and IDO by immunohistochemistry to evaluate whether they were correlated with subsequent treatment responses in breast cancer.Results: Expressions of IDO, CD33 + MDSCs and Foxp3 + Tregs were correlated with each other. Immunohistochemical double staining revealed that IDO expression in CD33 + MDSCs was positively correlated with Foxp3 + Tregs (P < 0.05). CD33 + MDSCs, Foxp3 + Tregs, and IDO expression in tumor tissues were associated with advanced clinical stage prior to NCT (P < 0.05). CD33 + MDSCs, Foxp3 + Tregs, IDO expression, IDO expression in CD33 + MDSCs and clinical T3–T4 stage prior to NCT, pathological T3–T4 stage, ER(+), luminal type were correlated with clinical responses of PD+SD (P < 0.05). Multivariate analysis showed that CD33 + MDSCs, IDO expression, IDO expression in CD33 + MDSCs, and advanced pathological T stage were risk factors for PD+SD. Focusing on the pCR of NCT, only CD33 + MDSCs, clinical T3–T4, and N1–N3 stage prior to NCT were associated with no-pCR (P < 0.05). The multivariate analysis showed that advanced clinical T stage and N stage were risk factors for no-pCR. Clinical stage prior to NCT were significantly correlated with progression free survival (P = 0.021), while Foxp3 + Tregs and clinical T stage were significantly correlated with overall survival (P = 0.022 and P = 0.001, respectively). Foxp3+Treg was significant risk factor for overall survival after adjusting covariates by COX regression.Conclusion: Tumor-infiltrating MDSCs, Tregs, IDO expression and IDO expression in MDSCs were correlated with clinicopathological features, NCT response, and prognosis of breast cancer patients, suggesting that they might be potential markers for clinical outcomes of NCT and help clinical decision-making for improved therapies for breast cancer.