Reprogramming macrophages toward M1-like phenotypes in the breast cancer microenvironment using mesenchymal stromal/stem cells: A review

Abstract

Breast cancer is the most common type of cancer in women worldwide and is the type of cancer with the most frequent high mortality rate for women in 110 countries. Treatment methods offered can have both short- and long-term effects on mobility, function, and quality of life. Improvement in treatment is essential to increase the survival rate and life expectancy. Macrophages in the breast cancer tumor microenvironment (TME) are known as tumor-associated macrophages (TAMs) and are the most common leukocyte population in mammary cancer. TAMs exhibit a phenotype similar to that of M2-like macrophages and secrete a variety of chemokines, cytokines, and growth factors, such as CCL2, CCL18, IL-10, VEGF, and PDGF, which are involved in cancer progression and metastasis and trigger drug resistance during cancer therapies. Hence, high infiltration of TAMs in breast cancer patients is closely associated with a poor clinical prognosis. Mesenchymal stromal/stem cells (MSCs) have been demonstrated by various studies to modulate immunomodulatory responses and reprogramming of TAMs to M1-like macrophages. MSCs skew naïve macrophages to a proinflammatory M1-like polarized state, which can alter the TME landscape. Hence, reprogramming TAMS to an M1-like phenotype with MSCs is a good strategy to enhance commonly used immunotherapies for the improvement of clinical outcomes among cancer patients. This present review discusses the potential of targeting TAMs by reprogramming macrophages using MSCs to increase antitumor responses in breast cancer.