Table 1.

Compounds targeting MDSCs

Strategy	Compound	Mechanisms of action	Clinical state	Reference
Preventing the recruitment of MDSCs	AZ13381758 (CXCR2 SM)	Inhibition of CXCR2	Trial in mice bearing pancreatic tumors	64
	TG100-115	Inhibition of PI3-kinase isoform p110γ	Trial in mice bearing tumors	65
	Zoledronate	Inhibition of MMP-9 activity	FDA approved for multiple cancers	82
	1α,25-Dihydroxyvitamin D3	Inhibition of IL6/p-STAT3	Trial in mice bearing esophageal squamous cell carcinoma	83
	Bevacizumab	Blocking of VEGF signaling	FDA approved for multiple cancers	84
	SX-682	Inhibition of CXCR2 signaling	Phase I trial in melanoma	85
	Sema4D mAb	Inhibition of MAPK-dependent chemokines such as CXCL1, 2, and 5	Trial in mice bearing oral cancer	86
	VPA	Inhibition of HDAC activity and downregulation of CCR2	FDA approved for multiple cancers	87
Promoting the differentiation of MDSCs into mature cells	Icariin and ICT	Downregulation of S100A8/9, STAT3, and AKT	Phase I trial in solid tumors; Phase III trial in hepatocellular carcinoma	69
	ATRA	Activation of ERK1/2 and upregulation of the ROS scavenger GSH	Phase II and Phase III trials in multiple cancers; Phase IV trial in acute promyelocytic leukemia	70
	ATX	Activation of the Nrf2 signaling pathway to induce the synthesis of GSH	Early Phase I trial in healthy volunteers; trial in mice bearing colon tumors	71
	Curcumin	Inhibition of activation of NF-κB and STAT3 signaling	Phase II and Phase III trials in multiple cancers	88
	MPSSS	Stimulation of the Myd88-dependent NF-κB signaling pathway	Trial in mice bearing tumor	89
	Docetaxel	Decrease in pSTAT3 in MDSCs	FDA approved for multiple cancers	90
	WGP	Activation of dectin-1 receptor	Phase II trial in non-small cell lung cancer	91
	HDC	Inhibition of NOX2	Phase IV trial in acute myeloid leukemia	92
Depleting MDSCs in the circulation and tumor infiltration	Anti-Ly6G mAb; anti-Ly6C mAb	Depletion of MDSCs	Trials in mice bearing multiple types of tumors	61
	BI 836858	Depletion of MDSCs by ADCC	Phase I trial in acute myeloid leukemia	74
	Doxorubicin	Triggering of the apoptosis program of MDSCs	FDA approved for multiple cancers	75
	Gemcitabine	Induction of MDSC apoptosis and necrosis	FDA approved for multiple cancers	76
	5-FU	Activation of caspase-3 and caspase-7 to induce MDSC apoptosis	FDA approved for multiple cancers	77
	Celecoxib	Inhibition of COX-2 and decrease in ROS	FDA approved for multiple cancers	93
	RGX-104	Promotion of MDSC apoptosis	Phase I trial in malignant neoplasms	94
	Anti-IL4Rα aptamer	Inhibition of IL-4Rα–STAT6 signaling	Trial in mice bearing mammary carcinoma	95
	Peptibody	Depletion of MDSCs by complement-dependent cytotoxicity or ADCC and induction of MDSC apoptosis	Trials in mice bearing multiple types of tumors	96
	DS-8273a	Induction of MDSC apoptosis by agonist of TRAIL-R2	Phase I trial in patients with advanced cancers	97
Inhibiting the elimination of L-arginine mediated by MDSCs	Phenformin	Decrease in the levels of ARG1 and S100A8/A9	Phase I trial in melanoma	98
	LPS	Interference with the HMGB1-TLR4 axis	Phase I and Phase II trials in lymphoma	99
	DMBG	Neutralization of the glycosylation function of methylglyoxal	Trial in melanoma-bearing mice	100
Inhibiting the activation of IDO in MDSCs	Indoximod	Inhibition of IDO	Phase III trials in multiple cancers	101
	Navoximod	Inhibition of IDO	Phase I trial in patients with recurrent/advanced solid tumors	101
	Epacadostat	Inhibition of IDO	Phase III trial in multiple cancers	101
	BMS-986205	Inhibition of IDO	Phase I and Phase II trials in melanoma; Phase I trial in various other types of advanced tumors	101
	1-MT	Inhibition of IDO	Phase I and Phase II trials in multiple cancers	34
Decreasing the levels of ROS and RNS in MDSCs	Sildenafil	Downregulation of ARG1 and NOS2 expression	FDA approved for multiple cancers	78
	CDDO-Me	Inhibition of STAT3 activity, upregulation of antioxidant genes, and decrease in ROS	Phase I and Phase II trials in multiple cancers	81
	AT38	Downregulation of ARG1 and NOS2, and decrease in RNS and N-CCL2	Trials in mice bearing multiple types of tumors	39
	NAC	Inhibition of ROS production	Phase I trial in multiple cancers; Phase II trial in patients at risk of melanoma	102
	WA	Decrease in TNFα, IL6, IL10, and ROS	Trials in mice bearing multiple types of tumors	103
	Entinostat	Decrease in ARG1, iNOS, and COX2	Phase I and Phase II trials in multiple cancers; Phase III trial in breast carcinoma	104
	IPI-145	Inhibition of PI3Kδ and PI3Kγ	Phase I and Phase II trials in head and neck squamous cell carcinoma; Phase III trial in lymphoma	105

VPA, valproic acid; CCR2, CC-chemokine receptor 2; ATRA, all-trans retinoic acid; ATX, astaxanthin; WGP, whole β-glucan particles; HDC, histamine dihydrochloride; ADCC, antibody-dependent cellular cytotoxicity; 5-FU, 5-fluorouracil; LPS, lipopolysaccharides; DMBG, dimethylbiguanide; 1-MT, 1-methyl-L-tryptophan; NAC, N-acetylcysteine; WA, Withaferin A.