The role of macrophages in the tumor microenvironment and tumor metabolism

The complexity and plasticity of the tumor microenvironment (TME) make it difficult to fully understand the intratumoral regulation of different cell types and their activities. Macrophages play a crucial role in the signaling dynamics of the TME. Among the different subtypes of macrophages, tumor-associated macrophages (TAMs) are often associated with poor prognosis, although some subtypes of TAMs can at the same time improve treatment responsiveness and lead to favorable clinical outcomes. TAMs are key regulators of cancer cell proliferation, metastasis, angiogenesis, extracellular matrix remodeling, tumor metabolism, and importantly immunosuppression in the TME by modulating various chemokines, cytokines, and growth factors. TAMs have been identified as a key contributor to resistance to chemotherapy and cancer immunotherapy. In this review article, we aim to discuss the mechanisms by which TAMs regulate innate and adaptive immune signaling in the TME and summarize recent preclinical research on the development of therapeutics targeting TAMs and tumor metabolism.

Automated summary

The complexity and plasticity of the tumor microenvironment make it challenging to comprehend the intratumoral regulation of different cell types and their activities. Tumor-associated macrophages (TAMs), a subtype of macrophages, have a significant impact on the signaling dynamics of the tumor microenvironment. TAMs play a crucial role in regulating cancer cell activities, immunosuppression, and resistance to chemotherapy and immunotherapy. This review focuses on the mechanisms by which TAMs modulate immune signaling in the tumor microenvironment and recent preclinical research on developing therapeutics targeting TAMs and tumor metabolism.