Table 1.

Summary of current strategies targeting myeloid cells in clinic

Function	Target molecule [Ref]	Agents	Total # trials		Combination agents	Tumor types	Trial phases
			Monotherapy	Combination
Proliferation, differentiation, and recruitment	CCR2 [165–172]	BMS-8113160	0	5	PD-1, chemotherapy, radiation, vaccine	CRC, hepatic, lung, pancreatic, renal	1/2, 2
	CSF1R [173–186]	Axatilimab, Emactuzumab, Bezuclastinib, Pexidartinib, Cabiralizumab, Lacnotuzumab, PD-0360324, IMC-CS4	5	14	BRAF, MEK, mTOR, PD-L1, PD-1, TKI, VEGF-A, chemotherapy, radiation, vaccine	Biliary, breast, fallopian, GIST, H&N, mastocytosis, melanoma, myeloid, lymphoma, ovarian, pancreatic, peritoneal, sarcoma, solid	1, 1/2, 2, 3
	CXCR1/2 [187–193]	SX-682, AZD5069, Navarixin	1	7	ADT, CTLA-4, PD-1, PD-L1, TGFβ-β, vaccine	CRC, melanoma, myeloid, pancreatic, prostate, solid	1, 1/2, 2
	FLT3 [68, 194–200]	CXD-301	0	11	CD40, PD-1, TLR3, chemotherapy, radiation, vaccine	Breast, H&N, lung, lymphoma, melanoma, prostate, solid	1, 1/2, 2
	STAT3 [201–208]	Danvatirsen, WP1066, TTI-101, OPB-111077, Napabucasin	4	9	Bcl-2, CTLA-4, DNMT, PD-L1, chemotherapy, radiation	Bladder, CNS, CRC, lung, lymphoma, melanoma, myeloid, pancreatic, solid	1, 1/2, 2, 3
	Siglec-15 [401–408]	NC318*	1	1	PD-1	Lung, solid	1/2, 2
	TREM2 [409–413]	PY314*	0	1	PD-1	Solid	1
Functional blockade	CD47 [209–215, 217, 218, 220, 221]	Magrolimab, Evorpacept, CC-90002, SRF231 Letaplimab, Lemzoparlimab, AO-176, TJ011133, SHR-1603, ZL-1201	3	18	Bcl-2, CCR4, CD20, CD38, DNMT, E3 ligase, GD2, PD-1, PD-L1, proteasome, VEGF-A, chemotherapy	GU, lymphoma, malignant heme, myeloma, myeloid, neuroblastoma, osteosarcoma, solid	1, 1/2, 2, 3
	SIRPɑ [209, 210, 212, 214, 216, 219, 222]	GS-0189, CC-95251, BI765063, TTI-621, TTI-622, Evorpacept, TG-1801, IMM0306, SL-172154, HX009, IBI322	10	21	Bcl-2, CD20, CD38, DNMT, E3 ligase, HER2, PD-1, proteasome, VEGFR2, chemotherapy, radiation	Cancer, CRC, esophageal, fallopian, gastric, H&N, lymphoma, malignant heme, myeloma, myeloid, ovarian, peritoneal, sarcoma, solid,	1, 1/2, 2, 2/3
Polarization	TLR9 [235–243]	CpG, CpG-STAT3 siRNA CAS3/SS3, CMP-001, Tilsotolimod, SD-101	1	16	4-1BB, ADT, BTK, CTLA-4, GnRH, OX-40, PD-1, PD-L1, radiation	Biliary, breast, CRC, hepatic, lymphoma, melanoma, pancreatic, prostate, solid	1, 1/2, 2
	CD40 [245–257]	Selicrelumab, Mitazalimab, CDX-1140, 2141-V11, Sotigalimab*, Dacetuzumab, Medi5068, ChiLob7/4, SEA-CD40, LOAd703, NG-350A	7	26	CD3, CSF1R, CTLA-4, EGFR, FLT3L, PD-1, PD-L1, TLR3, VEGF-A, chemotherapy, radiation, cellular therapies	Bladder, breast, CNS, CRC, esophageal, gastric, GI, lung, lymphoma, melanoma, ovarian, pancreatic, renal, sarcoma, solid,	1, 1/2, 2
	PI3Kγ [258–269]	Eganelisib*	1	3	PD-1, PD-L1, VEGF-A, chemotherapy	Breast, H&N, renal, solid	1, 2
	LILRB2 [425–430]	MK-4830, JTX 8064, IO-108	0	11	CTLA-4, PD-1, TIGIT, vaccine	CRC, lung, melanoma, renal, solid	1, 1/2, 2
	CLEVER-1 [431–435]	Bexmarilimab	2	1	PD-1	CRC, lung, renal, solid	1, 1/2
Metabolic reprogramming	CD73 [271–279]	Quemliclustat, LY3475070, Oleclumab, Mupadolimab, Sym021, IBI325, JAB-BX102, INCA00186, Uliledlimab*, NZV930, BMS-986179, HLX23, AK119, GS-1423	2	34	A2AR, A2BR, CTLA-4, EGFR, NKG2A, PD-1, PD-L1, VEGF-A, chemotherapy, radiation	Bladder, breast, CRC, lung, pancreatic, prostate, sarcoma, solid	1, 1/2, 2, 3
	CD39 [275, 277, 280, 281]	TTX-030, SRF617, IPH5201, ES002	0	5	A2AR, A2BR, CD73, PD-1, chemotherapy	Lymphoma, prostate, solid	1, 2
	A2AR [283–285]	Taminadenant, Ciforadenant, AZD4635*, Inupadenant	1	14	ADT, CD38, CD73, HIF2α, LAG3, PD-1, PD-L1, TIGIT, chemotherapy	Breast, lung, lymphoma, myeloma, prostate, renal, solid	1, 1/2, 2
	A2BR [283]	PBF-1129	1	1	PD-1	Lung	1
	A2AR A2BR [286]	Etrumadenant	0	11	ADT, CD39, CD73, IL-6, PD-1, PD-L1, TIGIT, VEGF-A, chemotherapy	CRC, H&N, lung, pancreatic, prostate	1, 1/2, 2
	IDO1 [287–291]	Epacadostat*, BMS-986205, KHK2455 navoximod, EOS200271, LY3381916, MK-7162	1	22	IL-15, LAG3, mTOR, PD-1, PD-L1, TGFβ-β, VEGF-A, chemotherapy, radiation, vaccine	Bladder, CNS, CRC, endometrial, fallopian, gastric, H&N, pancreatic, peritoneal, prostate, solid, urothelial	1, 1/2, 2, 3
Epigenetic reprogramming	HDAC [297, 299–309]	Entinostat*, Romidepsin, Tucidinostat, Mocetinostat, Domatinostat, Vorinostat*, Belinostat, Abexinostat, Panobinostat, Givinostat, Resminostat, Ricolinostat	17	147	AI, Bcl-2, BET, BTK, CD30, CD38, CDK 4/6, CTLA-4, DNMT, DRD2, E3 ligase, ER, GD2, GnRH, IL-2, IL-12, JAK, MEK, mTOR, NAE, ODC, PARP, PI3K, proteasome, PD-1, PD-L1, RT, TGFβ-β, TKI, VEGF-A, chemotherapy, radiation, cellular therapies	ALL, anal, bladder, breast, cervical, CNS, CRC, esophageal, fallopian, gastric, H&N, lung, lymphoma, melanoma, Merkel, MPN, myeloid, myeloma, neuroendocrine, ovarian, pancreatic, penile, peritoneal, prostate, renal, sarcoma, solid, urothelial, vulvar	1, 1/2, 2, 2/3, 3
Cytokines	STING [311, 312, 314–317]	BMS-986301, E7766, Ulevostinag, MK-2118, GSK3745417, TAK-676, SB11285, IMSA101 IACS-8803*, MIW815	1	9	CTLA-4, PD-1, PD-L1, radiation	Breast, H&N, lymphoma, solid	1, 1/2, 2
	IFNγ [319–322]	IFNγ 1b	1	2	HER2, PD-1, chemotherapy	Breast, lymphoma, myeloid, sarcoma	1, 1/2, 2
	IL-12 [323–333]	M9241*, GEN-1*, MEDI1191*, SAR441000	0	9	ADT, PARP, PD-1, PD-L1, TGF-β, chemotherapy, radiation	Breast, GU, lymphoma, ovarian, prostate, solid	1, 1/2, 2
	TNFR2 [334–343]	HFB200301, BI-1808, APX601, BITR2101, SIM0235	2	0	N/A	Solid	1, 1/2
	IL-1β [344–349]	Canakinumab, Anakinra, Gevokizumab	7	14	EPO, LAG3, PD-1, PD-L1, TIM-3, TKI, VEGF-A, VEGFR2, chemotherapy, radiation, cellular therapies	Breast, CRC, CLL, esophageal, gastric, lung, lymphoma, melanoma, myeloid, myeloma, pancreatic, prostate, renal	1, 1/2, 2, 3
	IL-6 [351, 353–356]	Tocilizumab, Sarilumab, Siltuximab*, Sirukumab, Olokizumab, Clazakizumab	0	10	CD3, CEA, CTLA-4, HER2, PD-1, PD-L1, chemotherapy, radiation	Breast, GU, lung, melanoma, pancreatic	1, 1/2, 2
	IL-8 [192, 193]	HuMax-IL8,	0	8	CDA, CTLA-4, DNMT, PD-1, radiation	H&N, hepatic, lung, myeloid, pancreatic, prostate, solid	1, 1/2, 2
	IL-10 [357–363]	Pegilodecakin	0	1	PD-1, TKI, chemotherapy	Solid	1
	TGFβ [364–370]	TASO-001, Galunisertib, Vactosertib, LY3200882, PF-06952229, AVID200, ABBV-151, SAR439459, NIS793, BCA101 trabedersen, ISTH0036, gemogenovatucel-T, belagenpumatucel-L, A83-01, SB-43-1542, RepSox, SM16, Bintrafup alfa, XPA-42-089	4	28	ADT, CD38, CDK 4/6, E3 ligase, IL-2, JAK, PD-1, PD-L1, TIM-3, VEGF-A, VEGFR2, chemotherapy, radiation	Breast, CNS, CRC, esophageal, hepatic, gastric, H&N, lung, MPN, myeloid, myeloma, ovarian, pancreatic, prostate, solid, urothelial	1, 1/2, 2, 3

*Indicates potentially significant results in clinical setting