Reprogramming of tumor-associated macrophages by metabolites generated from tumor microenvironment

Anim Cells Syst (Seoul). 2024 Apr 3;28(1):123-136. doi: 10.1080/19768354.2024.2336249. eCollection 2024.

Abstract

The tumor microenvironment comprises both tumor and non-tumor stromal cells, including tumor-associated macrophages (TAMs), endothelial cells, and carcinoma-associated fibroblasts. TAMs, major components of non-tumor stromal cells, play a crucial role in creating an immunosuppressive environment by releasing cytokines, chemokines, growth factors, and immune checkpoint proteins that inhibit T cell activity. During tumors develop, cancer cells release various mediators, including chemokines and metabolites, that recruit monocytes to infiltrate tumor tissues and subsequently induce an M2-like phenotype and tumor-promoting properties. Metabolites are often overlooked as metabolic waste or detoxification products but may contribute to TAM polarization. Furthermore, macrophages display a high degree of plasticity among immune cells in the tumor microenvironment, enabling them to either inhibit or facilitate cancer progression. Therefore, TAM-targeting has emerged as a promising strategy in tumor immunotherapy. This review provides an overview of multiple representative metabolites involved in TAM phenotypes, focusing on their role in pro-tumoral polarization of M2.

Keywords: Cancer; TAM; metabolites; polarization; tumor microenvironment.

Publication types

  • Review

Grants and funding

This study was supported by the National Research Foundation of Korea (NRF) [grant numbers: NRF-2022R1F1A1069937 (S.W.K.), NRF-2021R1A2C1012480 (Y-A. M.), and NRF-2022R1F1A1073025 (H.S.K.)]; and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea [grant number: HI22C1989].