Table 1.

Summary of the targetable enzymes that modulate the activation status of moDCs

DC signal potentiated	Pathway	Enzyme(s) targeted	Compound	Readout	References
Antigen presentation	Mevalonate	HMG-CoA reductase	Simvastatin (FDA approved as lipid-lowering medication)	↑ Surface MHC I:Ag. complex ↑ Surface MHC II:Ag. Complex In vivo efficacy against B16 (OVA) melanoma	[46]
	Mevalonate	GGPP synthase	TH-Z145	↑ Surface MHC I:Ag. complex ↑ Surface MHC II:Ag. Complex In vivo efficacy against B16 (OVA) melanoma	[46]
	Mevalonate	FPP synthase	TH-Z93	↑ Surface MHC I:Ag. complex ↑ Surface MHC II:Ag. Complex In vivo efficacy against B16 (OVA) melanoma	[46]
Co-receptors	PI3K/AKT	AKT	MK2206	↑ Surface MHC I ↑ CCR7	[59]
	DNA-PK	DNA-PK	NU7441	↑ Surface MHC I ↓ PD-L1/2	[59]
	MAPK	MEK	Trametinib (FDA approved for metastatic NSCLC)	↑ Surface MHC I	[59]
	PI3K/AKT  + DNA-PK  + MAPK	AKT  + DNA-PK  + MEK	MK2206  + NU7441  + Trametinib	↑ Surface MHC I ↑ CCR7 ↓ PD-L1/2 ↑ CD40, CD83, CD86 ↑ In vivo efficacy versus U87 GBM	[59]
	MAPK	P38	SB202190	↑ OX40L ↑ In vivo efficacy versus B16 (OVA) melanoma	[64]
Cytokines	JAK/STAT/ PTPs	PTPN1 PTPN2	L598	moDC differentiation: ↑ Surface MHC I & II, CD40, CD80, CD86 ↑ IL-12p70 and IFN-γ	[69]
	JAK/STAT/ SOCS	SOCS1	SOCS1 siRNA	↑ IL-12p70	[72]
	Autocrine IL-10 signaling	BTK	Ibrutinib (FDA approved for various leukemias and lymphomas)	↑ Surface MHC II ↑ CD80	[78]
	BTK-IDO-GATOR2-mTOR	BTK  + IDO	Ibrutinib  + indoximod	↑ moDC differentiation toward cDC1 phenotype ↑ In vivo efficacy versus B16F10 and EL4-OVA	[79]