Figure 5.

Targeting macrophages to control tumor microenvironment. Therapeutic strategies aimed at controlling TAM in the TME fall into 1) controlling the number of TAMs either by anti-CSF-1R and chemicals such as clodronate, zoledronic acid, and Trabectedin to deplete the cells, or by chemokine blockades to decrease the recruitment of TAMs. 2) Functional-based reprogramming that targets the surface receptors/ligands. For example, increase phagocytosis by SIRPα, Siglec-10, and LILRB1/2 blockades; activate TLR and CD40 signaling by agonists; inhibit immunosuppression by targeting Trem2, CD163, and PD-L1. 3) Pan reprogramming that inhibits the intracellular key regulators such as PI3Kγ and HDAC to prevent TAM polarization. 4) Expression of engineered CAR in TAMs to recognize and phagocytose targeted tumor cells.