M2 macrophages predict response to neoadjuvant chemotherapy in triple negative breast cancer patients

Macrophages, the predominant immune-related stromal cells within tumor microenvironment, could be polarized into M1 and alternative M2 macrophages. M1 macrophages are pro-inflammatory and eliminate cancer cells, whereas M2 macrophages are immunosuppressive and facilitate tumor growth. Mounting evidence has shown that M2 macrophages are responsible for a poor prognosis in triple negative breast cancer (TNBC) patients. Since neoadjuvant chemotherapy is becoming the foundation treatment for TNBC, the relationship between M2 macrophages and response to neoadjuvant chemotherapy remains to be elucidated. Infiltration of M2 macrophages were checked by analyzing the CD163 levels on surgical resection specimens from 42 Chinese TNBC patients treated with neoadjuvant chemotherapy. Evaluation of M2 macrophages together with other immune markers including CD8-positive cytotoxic T cells and PD-L1 expression in TNBC and its association with pCR after neoadjuvant chemotherapy were performed. Pathological complete response (pCR) was significantly associated with younger age, higher tumor or stromal PD-L1 expression, higher levels of tumor or stromal CD8-positive cytotoxic T cells, but lower infiltration of CD163-positive M2 macrophages, with the level of CD163-positive M2 macrophages in stromal area as the strongest factor. Our study showed that high infiltration of CD163-positive M2 macrophages was negatively associated with the chemotherapeutic response to neoadjuvant chemotherapy in Chinese TNBC patients and could be used as a promising prognostic candidate for Chinese TNBC patients treated with neoadjuvant chemotherapy.