Table 1.

FDA‐approved agents with reported effects on human MDSCs

Agent	FDA‐approved indications	Agent classification	General mechanism of action	Effects on human MDSCs	Effects on patient outcome in approved indication	Refs. for MDSC activity
ATRA	APL	Differentiating agent	Binds ERK1/2 and RARs; ↑GSH synthase; ↑GSH; ↓ROS	Reduces frequency of circulating total and mo‐MDSCs by differentiating cells into mature myeloid cells	↑OS; ↑PFS; ↑RR	[12, 14, 15]
Vitamin D	Secondary hypoparathy‐ and hyperparathy‐roidism	Differentiating agent	Inhibits ERK signaling and promotes apoptosis via up‐regulation of BAX	Reduces frequency of circulating CD34Pos MDSC by differentiating cells into mature myeloid cells	Unknown; currently in clinical trials for cancer treatment	[25, 26–27]
Sunitinib	RCC, GIST, and PNET	RTK inhibitor	Inhibits activity of RTKs, including PDGFR and VEGFR	Restricts MDSC development; reduces number and/or suppressive function of circulating total and PMN‐MDSCs	↑OS; ↑PFS; ↑RR (RCC and GIST)	[35, 37]
Bevacizumab	Colon and several other cancers	Angiogenesis inhibitor	Inhibits angiogenesis by inhibiting VEGF binding to VEGFR	Decreases circulating total and KITPos MDSC frequency	↑PFS; ↑OS (cervical and colon cancer)	[42, 43]
Tadalafil	ED and BPH	PDE5 inhibitor	NO and arginase inhibition; ↓Arg1 expression; ↓NOS2 expression; ↓ iNOS expression; catalyzes the hydrolysis of cGMP [7]; ↑ intracellular [cGMP]; ↑NO2; ↑penile BP	Reduces number and/or suppressive function of bone marrow and circulating total and mo‐MDSCs	Unknown; currently in clinical trials for cancer treatment	[52, 53, 56]
Ipilimumab	Melanoma	Check‐point inhibitor	CTLA‐4 antibody promotes immune activation.	Reduces frequency of circulating PMN‐MDSC	↑OS; ↓ROP; ↑RR; ↑disease control rate	[71, 72]
				Reduces the number of ARG1+ myeloid cells
Vemurafenib	Melanoma with BRAF V600E mutations	B‐raf/Mek inhibitor	Inhibits mutated B‐RAF	Indirect action; reduces frequency of circulating mo‐MDSC	↑OS; ↓ROP; ↑RR; ↑PFS	[75]
			↓IL‐6; ↓IL‐10; ↓VEGF production by the tumor