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

Dawei Shou,Qiming Sun,Weihua Gong,Zhenya Song,Jian Yin,Liang Wen

doi:10.18632/oncotarget.11352

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 tumor-favoring 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 MDSC-targeted 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.

Highlights

Breast cancer is one of the major types of cancer in women, accounting for many cancer related deaths in women [1]
It has been reported that 1-methyl-L-tryptophan (1-MT) can inhibit Myeloid-derived suppressor cells (MDSCs)-produced IDO to suppress the inhibitory effect of MDSCs on T cells, which could help to promote the treatment of breast cancer [8]
There are many methods to tackle with the impact of MDSCs, including reduction of MDSCs and inhibition of their functions

Summary

Introduction

Breast cancer is one of the major types of cancer in women, accounting for many cancer related deaths in women [1]. Breast cancer cells can recruit tumor-infiltrating leukocytes, including regulatory T cells (Treg), MDSCs and type 2 macrophages, to form a tumor-promoting microenvironment, which downregulates the anti-tumor immunity [13]. Breast cancer cells can induce the accumulation of MDSCs from bone marrow to a local tumor site in several ways, including cancer-derived cytokines and chemokines.

Results

Conclusion