Abstract 4349: C-C chemokine receptor 2-positive monocytic myeloid-derived suppressor cells predicts chemotherapeutic responses of the metastatic lesions in breast cancer patients

Abstract

Abstract Anti-tumoral T cell immunity is counterbalanced by several types of immunosuppressive cells such as Myeloid-Derived Suppressor Cells (MDSC). Circulating MDSC levels correlate with poor prognosis and metastatic progression of breast cancer patients. However, the value of MDSC in predicting chemotherapeutic treatment responses in the metastatic lesions is not clearly understood. We performed a prospective cohort clinical study to measure MDSC before and after chemotherapy in metastatic breast cancer patients (N=64). Multicolor flow cytometry was used to quantitate two major subtypes, i.e. monocytic (M-) and polymorphonuclear (PMN-) MDSC, and one additional subtype, C-C chemokine receptor 2 (CCR2)-positive M-MDSC in the fresh peripheral blood mononuclear cells. M-MDSC were defined as HLA-DRlow/−CD45+CD11b+CD15−CD14+ PBMC, and PMN-MDSC were defined as CD45+CD11b+CD33+CD15+ CD14− PBMC. PMN-MDSC and CCR2+ M-MDSC, but not M-MDSC, were significantly increased after chemotherapy. Subsequently, we divided the patients by two groups (therapy-sensitive vs. -resistant groups) by treatment responses. Treatment-resistant patients had significantly increased CCR2+ M-MDSC. Unsupervised clustering of patients based on MDSCs populations dichotomized patients PMN-MDSC high or M-MDSC high groups. M-MDSC high patients had increased bone and lymph node metastasis. In addition, CCR2+ M-MDSC levels correlated with the progression-free survival (P<0.05). Altogether, our results showed that CCR2+ M-MDSC levels potentially predict the therapeutic responses in the metastatic lesions of breast cancer patients. Citation Format: Ju Won Kim, Jason K. Sa, Seung Pil Jung, Kyong Hwa Park, Serk In Park. C-C chemokine receptor 2-positive monocytic myeloid-derived suppressor cells predicts chemotherapeutic responses of the metastatic lesions in breast cancer patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4349.