Table 1.

Information about Targeted therapy for tumor-associated macrophages.

Strategy	Method	Mechanism	Medication route	Effect on macrophages	Effect on tumor	Reference
TAM depletion	PLX3397+cediranib	CSF-1R + VEGFR2 inhibition	Oral	Reshape TAMs and reduce angiogenesis function	Decrease vessel density and cell proliferation	24
	BLZ945 + OSI906	CSF-1R + IGF-1R inhibition	Oral	Downregulate M2-like gene and IGF in BMDMs	Overcome tumor resistance to CSF-1R blockade therapy	22
	NE-siRNA-CD73	CD73 inhibition	Nasal	Reduce Tregs, microglia, and macrophages	Induce tumor cell apoptosis	25
	CCX872/Anti-PD-1	CCL2/CCR2 axis disruption	Oral	Reduce tumor-associated MDSCs and activate T cells	Enhance Anti-PD-1 therapy and prolong survival	29
	Celecoxib	CCL2 and CXCL10 inhibition	Oral	Reduce microglia and macrophages	Induce apoptosis, inhibits GSC viability	28
	CCR2 knockout	CCL2/CCR2 axis disruption	–	Decrease TAM infiltration	Enhance tumor proliferation and vascular integrity	30
	TG100–115	PI3Kγ inhibition	Intraperitoneal	Suppresses microglia/TAM accumulation and secretion of IL-11	Suppress tumor genesis and TMZ resistance	35
	lncRNA-miRNA- ALKBH5	Regulate ALKBH5 expression	Subcutaneous	Reduce M2-like cell infiltration	Suppress tumor proliferation	33
	CDX-LIPO	Targeting PI3K/mTOR	Intravenous	promote M1-like polarization	Induce autophagy and immunogenic cell death	36
	LY2228820	p38 MAPK inhibitor	Intraperitoneal	Inhibit macrophage aggregation	Suppress tumor proliferation	37
TAM re-education	Anti-PD-L1+radiation	Inhibit PD-L1 pathway+abscopal response	–	Activate macrophages, enhance phagocytosis	Prolong survival	46
	PD-L1 knockout	Inhibit PD-L1 pathway	–	Upregulate M1-like and downregulate M2-like populations	Inhibits proliferation and invasion	44
	Nivolumab/Bevacizumab	Inhibit PD-L1 pathway	Oral	Regulate TAM polarization	Prolong survival	43
	α-lactose	Gal-9/ Tim-3 blockade	Intraperitoneal	Inhibit M2-like polarization	Inhibit angiogenesis and tumor proliferation	50
	Anti–Tim-3 antibody	Gal-9/ Tim-3 blockade	Intravenous	Inhibit M2-like polarization	Inhibit angiogenesis and tumor proliferation	50
	LGALS9- targeted shRNAs	Gal-9/ Tim-3 blockade	In vitro	Inhibit M2-like polarization	Inhibit angiogenesis and tumor proliferation	50
	mRNA-NPs	IRF5/IKKβ expression	Intravenous	increase M1-like cell and decrease M2-like cells	Suppressed tumor progression and prolong survival	52
	CpG-Au-NPs	Enhance radio, re-polarize M2	Intratumoral	Increase M1-like cell and decrease M2-like cells	Enhance tumor killing of ICB and radiotherapy	53
	CD40 agonist+IL-6 neutralize +ICB	Macrophage activating	Orthotopic injection	Reverse immunosuppression, activate T cell	Sensitize tumor to ICB and prolong survival	51
	miRNA-155 Nanogel	Mimic virus	Intravenous	Increase M1-like cell and decrease M2-like cells	Inhibits tumor proliferation and prolong survival	56
	ITGB3 siRNA/anti‐MFG‐E8 antibody	MFG-E8 pathway inhibition	Transfect	Reduce M2-like and increase M1-like microglia	Suppress tumor growth	57
Targeting pro-tumoral function of TAMs	Propofol + TMZ	Downregulate HIF-1α	Intraperitoneal	Enhances macrophage infiltration and inflammation	Reduce drug resistance, promote apoptosis	3
	OAT-1746	Inhibiting ARG1/2	Oral	Transform TAM gene expression signature to a pro-inflammatory phenotype	Improves the efficacy of the PD-1 checkpoint inhibition	63
	PLX5622	CSF-1/CSF-1R inhibition	Oral	Prevents hippocampal-dependent memory deficits	–	64
	BLZ-945	CSF-1/CSF-1R inhibition	Oral	Reduce microglia and MDM populations, reduce peritumoral macrophages	Enhances initial response to radiotherapy, inhibits tumor recurrence	66
	CCL8 neutralized antibody	Inhibit ERK1/2	Subcutaneous	Decrease macrophage-derived CCL8	Decreases TAM-induced glioma invasion	67
	Integrin and TGFβ-R1 blockade	Inhibit Src-PI3K-YAP pathway	In vitro	Inhibit endothelial cells-macrophage interaction	Inhibit tumor angiogenesis	68
	CYP2J2 shRNA	Restrained the release of 11,12-EET	In vitro	Inhibit EET expression on M2-like microglia	Inhibit tumor angiogenesis	69
	α-lactose	Gal-9/ Tim-3 blockade	Intraperitoneal	Inhibit secretion of VEGF	Inhibit angiogenesis and tumor proliferation	50
	BAY-218	Inhibit AhR	Intravenous	Reverse immunosuppression enhance the function of macrophages	Decrease tumor proliferation and prolong survival	70