Table 2.

Active clinical trials targeting MDSCs in human cancer treatments

Agent(s)	Type of cancer(s) tested	Agent classification	General mechanism of action	Proposed effects of human MDSCs	Trial number
Arginine‐rich nutritional supplement with surgery	Colon cancer	Differentiating agent	Increases availability of arginine	Reduces MDSC‐suppressive function	NCT01885728
Capecitabine + bevacizumab	Recurrent glioblastoma	Cytotoxic agent + VEGF inhibitor	Kills rapidly dividing cells and blocks angiogenesis	Capecitabine ↓MDSC number	NCT02669173
				Bevacizumab ↓MDSC‐mediated angiogenesis and possibly MDSC recruitment to the tumor
Cisplatin + CKM + celecoxib + DC vaccine versus cisplatin + celecoxib + DC vaccine	Ovarian cancer	COX‐2‐selective inhibitor + arginase inhibitor + chemokine modulator + cytotoxic agent	Celecoxib prevents COX‐2 from making PGs out of arachidonic acid, which regulates inflammation; COX‐2 inhibitors also function as arginase inhibitors; CKM may alter cell signaling; cisplatin kills rapidly dividing cells.	Celecoxib ↓MDSC‐suppressive function	NCT02432378
				Cisplatin ↓MDSC frequency
DC vaccine with or without gemcitabine	Sarcoma	Vaccine + nucleoside and cytotoxic agent	Gemcitabine is a nucleoside and kills rapidly dividing cells.	Gemcitabine ↓MDSC frequency	NCT01803152
EP4 antagonist, AAT‐007 (RQ‐07; CJ‐023,423) + gemcitabine	Prostate cancer, NSCLC, and breast cancer	EP4 antagonist, anti‐inflammatory	EP4 antagonist, anti‐inflammatory	AAT‐007 and gemcitabine are proposed to ↓MDSC frequency.	NCT02538432
Ipilimumab and ATRA	Stage IV melanoma	Immune check‐point inhibitor + differentiating agent	Ipilimumab is an anti‐CTLA‐4 mAb that alters T cell activation and proliferation and reduces Treg function; ATRA, a vitamin, up‐regulates GSH synthase, leading to increased intracellular concentrations of GSH and decreased ROS production.	ATRA ↓MDSC frequency and ↓suppressive function; ipilimumab improves anti‐tumor immune response	NCT02403778
5FU, leucovorin, bevacizumab + anakinra	Metastatic colorectal cancer	Cytotoxic agent + VEGF inhibitor + IL‐1R antagonist	LV5FU2 consists of leucovorin and 5FU, which kill rapidly dividing cells; bevacizumab inhibits VEGF disrupting cell signaling; anakinra is an IL‐1R antagonist	Bevacizumab ↓MDSC‐mediated angiogenesis and possibly MDSC recruitment to the tumor	NCT02090101
				5FU ↓MDSC frequency
PF‐04136309 + FOLFIRINOX	Pancreatic adenocarcinoma	CCR2 antagonist + a cytotoxic agent	PF‐04136309 inhibits the inflammatory response and metastasis in some tumors.	PF‐04136309 proposed to ↓MDSC trafficking to tumor.	NCT01413022
			FOLFIRINOX consists of leucovorin, fluorouracil, oxaliplatin, and irinotecan, which kill rapidly dividing cells.
PD‐L1 or PD‐1 inhibitor	NSCLC	Immune check‐point inhibitor	PD‐1 inhibitors bind the PD‐1 receptor and block it from binding with PD‐L1 and PD‐2 ligand; PD‐L1 inhibitors block the ligand for the PD‐1 receptor and B7‐1; both PD‐L1 and PD‐1 inhibitors result in T cell proliferation activation, cytokine production, and cell adhesion.	Proposed to ↓MDSC‐suppressive function	NCT02827344
Omaveloxolone (RTA‐408) in combination with ipilimumab or nivolumab	Melanoma	NRF2 activation + immune check‐point inhibitor	In mice, RTA‐408 reduces tumor nitrotyrosine burden, inhibits the activity of MDSCs, and augments T cell anticancer activity.	RTA‐408 proposed to ↓MDSC‐suppressive function.	NCT02259231
			Ipilimumab is an anti‐CTLA‐4 mAb that alters T cell activation and proliferation and reduces Treg function; nivolumab is an anti‐PD‐1 inhibitor.
Tadalafil	Squamous cell carcinoma	PDE5 inhibitor	NO and arginase inhibitor	↓MDSC frequency and suppressive function	NCT01697800
			Tadalafil: ↓Arg1 expression; ↓NO2 expression; ↓ iNOS expression
Tadalafil + anti‐ MUC‐1 vaccine	HNSCC	PDE5 inhibitor + vaccine	NO and arginase inhibitor.	↓MDSC frequency and suppressive function	NCT02544880
			Tadalafil: ↓Arg1 expression; ↓ΝΟ2 expression; ↓ iNOS expression

CKM, Chemokine modulatory regime; COX‐2, cyclooxygenase 2; EP4, PGE2 receptor 4; LV5FU2, leucovorin and fluorouracil combination; MUC‐1, mucin 1; NO2, nitrogen dioxide; PD‐L1, PD‐1 ligand; ↓, down‐regulates/decreases; ↑, up‐regulates/increases.