Natural products targeting macrophages in tumor microenvironment are a source of potential antitumor agents.

Background: Macrophages are one of the major cell types in the immune system and are closely related to tumor development, which can be polarized into M1 type with anti-tumor activity or M2 type with pro-tumor activity. The infiltration of more macrophages into tumor predicts poorer prognosis due to their more exhibition of M2 phenotype under the influence of many factors in the tumor microenvironment (TME). Therefore, reverse of M2 macrophage polarization in TME is conducive to the suppression of tumor deterioration and understanding the influencing factors of macrophage polarization is helpful to provide new ideas for the subsequent targeting macrophages for tumor therapy.

Purpose: This review summarizes the effects of TME on macrophage polarization and natural products against M2 macrophage polarization, which may provide some directions for tumor therapy.

Methods: The search of relevant literature was conducted using the PubMed, Science Direct, CNKI and Web of Science databases with the search terms "macrophage", "tumor microenvironment", "natural product" and "tumor".

Results: The mutual transformation of M1 and M2 phenotypes in macrophages is influenced by many factors. Tumor cells affect the polarization of macrophages by regulating the expression of genes and proteins and the secretion of cytokines. The expression of some genes or proteins in macrophages is also related to their own polarization. Many natural products can reverse M2 polarization of macrophages which has been summarized in this review.

Conclusion: Regulation of macrophage polarization in TME can inhibit tumor development, and natural products have the potential to impede tumor development by regulating macrophage polarization.