Table 3.

Clinical trials targeting myeloid cells in cancer

Cancer	Therapy	Target	Effect	MDSC Phenotype	Ref
Metastatic melanoma	Vemurafenib1	B-RAF inhibitor	Decrease in Gr-MDSC and Mo-MDSC	Mo-MDSC: CD14+ HLA-DR−/low Gr-MDSC: CD14− CD66b+ Arg+	(17)
Metastatic melanoma	Ipilimumab1	Anti – CTLA-4	Lower Mo-MDSC frequency correlated with a more positive response to immunotherapy	Mo-MDSC: Lin− CD14+ HLA-DR−/low	(85)
RCC	ATRA + IL-2	Various	Decreased MDSC frequency in blood	Lin− HLA−DR− CD33+	(104)
RCC	Sunitinib (Tyrosine kinase inhibitor)	VEGF PDGF c-kit CSF1R	Reduced MDSC and Treg; Impact on distinct MDSC populations is not clear: as CD33 is expressed on both subsets	Mo-MDSC: CD33+ HLA-DR− Gr-MDSC: CD14− CD15+	(105)
RCC	Sunitinib (Tyrosine kinase inhibitor)	VEGF PDGF c-kit CSF1R	Mo-MDSC decreased in frequency following treatment	Lin− HLA-DR−/low CD14+	(106)
HNSCC	25-hydroxyvitamin D3	Pleiotropic effects	Decreased CD34+ cells; increased HLA-DR, increased IL-12 and IFNγ in plasma, improved T-cell blasts	CD34+	(107)
SCLC	ATRA + Vaccine	Numerous targets	Decreased MDSC frequency ~2-fold in blood	Lin− HLA-DR− CD33+ or CD11b+ CD14− CD33+	(108)
PDA	Zoledronic acid	Farnesyl pyrophosphate synthase	No effect on Gr-MDSC in blood at doses studied	CD45+ Lin− CD11b+ CD33+ CD15+	(92)
PDA	CDDO-Me2 + gemcitabine	iNOS COX2 NFκB	No change in % MDSC; increased T cell proliferation	Lin− HLA-DR−/low CD33+ or Lin− CD14− CD11b+ CD33+	(109)
Multiple Myeloma3	PDE5 inhibitor (tadalafil)	iNOS Arg	Decreased iNOS, Arg, ROS, & nitrotyrosine; increased TCRζ expression and IFNγ	CD14+ IL-4R+	(110)

¹These therapies were not designed to target MDSC but did decrease MDSC frequency that correlated with disease response suggesting that MDSC number can be surrogate marker for therapeutic response.

²CDDO-Me:synthetic triterpenoid C-28 methyl ester of 2-cyano-3,12-dioxooleana-1,9,-dien-28-oic acid

³Case study