Therapeutic strategies targeting TAMs. (IMAGE)
Caption
Therapeutic strategies targeting TAMs. Currently, three primary strategies have been developed to target TAMs, aiming to achieve greater efficacy in tumor treatment. 1. TAM reduction: CSF-1R or CCR2/CCL2 inhibitors that block CSF-1R and CCR2/CCL2 axis to reduce the number of TAMs. In addition, clodronate liposomes induce apoptosis of TAMs, further decreasing abundance in the tumor microenvironment; 2. TAM repolarization: TLR7/8 agonists, CD40 agonists, and TREM2 antagonists can reprogram TAMs from a pro-tumor phenotype to an anti-tumor phenotype. Several metabolic targets, including LDHA, GLUT1, PFKFB3, LXR, Arg1, and IDO have shown potential for reshaping TAM phenotype and thereby modulating tumor progression; 3. Restoring “eat me” signals: Blocking the immune checkpoints, such as CD47-SIRPα, CD24-Siglec-10, and Siglec-3/15, can restore “eat me” signals and promote the phagocytic activity of TAMs against cancer cells. CCL2, C-C chemokine ligand 2; CCR2, C-C chemokine receptor type 2; CSF-1R, colony-stimulating factor 1 receptor; TLR7/8, Toll-like receptor 7/8; TREM2, triggering receptor expressed on myeloid cells 2. LXR, Liver X Receptor; LDHA, Lactate Dehydrogenase A; GLUT1 – Glucose Transporter 1; PFKFB3, 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 3; Arg1, Arginase 1; SIRPα – Signal Regulatory Protein α.
Credit
Cancer Biology & Medicine
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