Suppressive role of myeloid-derived suppressor cells (MDSCs) in the microenvironment of breast cancer and targeted immunotherapies

Abstract

Myeloid-derived suppressor cells (MDSCs) play a pivotal role in promoting tumor growth and metastasis and can even decrease the efficacy of immunotherapy. In breast cancer, MDSCs are recruited mainly by breast cancer cells to form a tumorfavoring microenvironment to suppress the anti-tumor immune response. In addition, MDSCs can react directly with breast cancer cells. In this paper, we describe several ways to recruit MDSCs in breast cancer, including breast cancer cell-derived cytokines and chemokines. The intracellular pathways in MDSCs during recruitment are classified as the STAT3-NF-κB-IDO pathway, the STAT3/IRF-8 pathway and the PTEN/Akt pathway. MDSCs act on T cells and NK cells to suppress the body's immunity, and via IL-6 trans-signaling, promote breast cancer directly. We further describe MDSCtargeted immune therapies for breast cancer, which are classified as: preventing the formation of MDSCs, eliminating MDSDCs, and reducing the products of MDSCs. Furthermore, MDSC-targeted immunotherapy potentiates the effect of the other immunotherapies. Based on the facts that MSDCs have significant roles in breast cancer malignant behaviors and can be suppressed by various strategies, we do believe MDSC-targeted immunotherapy presents a broad prospect in the future.