CD8+, CD4+ and FOXP3+ cell profiles and their change after neoadjuvant chemotherapy in patients with triple negative breast cancer

Abstract

Background: Neoadjuvant therapy for breast cancer has been increasingly used in recent years as first-line treatments for breast cancer. A high lymphocytic infiltration is known to correlate with response to neoadjuvant chemotherapy and prognosis, however little attention has been paid to changes in CD8+, CD4+, FOXP3+ immune call profiles during perioperative chemotherapy. Methods: Treatment results of 43 patients with TNBC stages IIB-IIIB homogeneously treated with neoadjuvant chemotherapy were analyzed. We studied the baseline and post-treatment FOXP3+, CD4+, CD8+tumor-infiltrating immune cells by immunohistochemistry. Therapeutic pathomorphism was evaluated in terms of the residual tumor burden identification (RCB) (using Miller-Payne classification). Variables distribution was scored using ANOVA test. Survival probabilities were estimated by the Kaplan-Meir method. Hazard ratios and their 95% confidence interval were calculated with the Cox proportional hazards model. Results: Pathological complete response (pCR) to neoadjuvant chemotherapy was identified in 12% of patients. In group without pCR high baseline levels of the stromal CD4+ cells were identified in 39,4% of patients, peritumoral CD4+ cells - in 44,7%; high levels of stromal CD8+ cells were identified in 28% and peritumoral CD8+ - in 52% of patients; and high levels of FOXP3+ were identified 47,3% of patients. The levels of CD8+ and FOP3+ cells decreased during treatment in 13% of patients. The levels of peritumoral CD4+cells deceased during treatment in 34,%of patient, whereas levels of stromal CD4+ increased during treatment in 10,6% of patients. We found that in the population with residual disease after neoadjuvant chemotherapy the high baseline levels of peritumoral CD4+ immune cells were strongly associated with adverse outcome (HR 3,33, CI 1,29 - 8,58; p=0,013). Conclusions: The high baseline levels of peritumoral CD4+ lymphocytes in triple negative breast cancer tumor failing to achieve pCR were associated with adverse outcome. Further studies are required for identifying patients who are likely to benefit from immunotherapeutic adjuvants to conventional treatment approaches.