Roles of M1 Macrophages and Their Extracellular Vesicles in Cancer Therapy

Abstract

Tumor-associated macrophages (TAMs) are inflammatory cells that are important components of the tumor microenvironment. TAMs are functionally heterogeneous and divided into two main subpopulations with distinct and opposite functions: M1 and M2 macrophages. The secretory function of TAMs is essential for combating infections, regulating immune responses, and promoting tissue repair. Extracellular vesicles (EVs) are nanovesicles that are secreted by cells. They play a crucial role in mediating intercellular information transfer between cells. EVs can be secreted by almost all types of cells, and they contain proteins, microRNAs, mRNAs, and even long non-coding RNAs (lncRNAs) that have been retained from the parental cell through the process of biogenesis. EVs can influence the function and behavior of target cells by delivering their contents, thus reflecting, to some extent, the characteristics of their parental cells. Here, we provide an overview of the role of M1 macrophages and their EVs in cancer therapy by exploring the impact of M1 macrophage-derived EVs (M1-EVs) on tumors by transferring small microRNAs. Additionally, we discuss the potential of M1-EVs as drug carriers and the possibility of reprogramming M2 macrophages into M1 macrophages for disease treatment. We propose that M1-EVs play a crucial role in cancer therapy by transferring microRNAs and loading them with drugs. Reprogramming M2 macrophages into M1 macrophages holds great promise in the treatment of cancers.

Keywords: M1 macrophage; M2 macrophage; cancer; exosome; extracellular vesicles.

Figure 1

The characteristics of M1 and M2 macrophages. (a) M1 Macrophage; (b) M2 macrophage. M1 macrophages were mainly activated by LPS and TNF-α and secreted pro-inflammatory factors. M1 macrophages are involved in immune activation, promoting apoptosis and phagocytosis of cancer cells. M2 macrophages were mainly activated by IL-4 and mainly secreted anti-inflammatory factors, with high expression of CD206 and enhanced endocytosis. M2 macrophages have anti-inflammatory activity and participate in wound damage repair, phagocytosis, and clearance of apoptotic cells.

Figure 2

M1-EVs function by microRNA transfer. M1-EVs delay and inhibit the progression of multiple cancers through microRNA transfer.

Figure 3

M1-EVs have shown better therapeutic efficacy as drug carriers in disease treatment. EVs produced by M1 macrophages can be used as novel drug carriers to encapsulate proteins, therapeutic RNAs, and small-molecule drugs to reach the lesion site. Compared with EVs alone or these drugs alone, EV-loaded drugs have better synergistic therapeutic effects.

Figure 4

Reprogramming of M2 macrophages into M1 macrophages. There are many ways to reprogram M2 macrophages into M1 macrophages, such as using antioxidants, natural materials, synthetic drugs, engineered EVs, photodynamic synthetic therapies, epigenetic therapies, and microRNAs.