Abstract
Besides transformed cells, the tumors are composed of various cell types that contribute to undesirable tumor progression. Tumor-associated macrophages (TAMs) are the most abundant innate immune cells in the tumor microenvironment (TME). Within the TME, TAMs exhibit high plasticity and undergo specific functional metabolic alterations according to the availability of tumor tissue oxygen and nutrients, thus further contributing to tumorigenesis and cancer progression. Here, we review the main functional TAM metabolic patterns influenced by TME, including glycolysis, amino acid, and fatty acid metabolism. Moreover, this review discusses antitumor immunotherapies that affect TAM functionality by inducing cell repolarizing and metabolic profiles towards an antitumoral phenotype. Also, new macrophage-based cell therapeutic technologies recently developed using chimeric antigen receptor bioengineering are exposed, which may overcome all solid tumor physical barriers impeding the current adoptive cell therapies and contribute to developing novel cancer immunotherapies.
Highlights
Tumor-associated macrophages (TAMs) and their precursors represent a large proportion of infiltrating myeloid cells in the microenvironment of most solid human malignancies, and they play a crucial role in tumorigenesis [1,2,3]
Tumor metabolic activities are critical for tumor growth and progression
TAMs are one of the critical noncancer cell populations that infiltrate tumors. They actively interact with cancer cells and may promote tumor growth by regulating antitumor immune function
Summary
Tumor-associated macrophages (TAMs) and their precursors represent a large proportion of infiltrating myeloid cells in the microenvironment of most solid human malignancies, and they play a crucial role in tumorigenesis [1,2,3]. TAMs infiltrate hypoxic regions, in part, being attracted by several chemotactic signals secreted by cancer cells due to low oxygen pressure. Upon arrival, they suffer a reduction in motility and accumulate at ischemic tumor sites, which may explain the high TAM density in hypoxic and necrotic TME areas of some types of cancers [7, 8]. This may contribute to the promotion of tumor growth and progression. Because of the protumorigenic role of TAMs in cancer, we present primary therapies targeting TAMs, including small drugs, combinations with immune-checkpoint inhibitors (ICI), and the current strategy of the chimeric antigen receptor (CAR) to engineer macrophages towards the adoption of antitumor functions
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