Table 1

Clinical trials combining immune checkpoint blockade and drugs that may affect resistance linked with neutrophil biology

	Target	Drug	Immune checkpoint inhibitor	Clincal trial	Cancer type	Phase
	DPP8, DPP9, and FAP inhibitor	Talabostat	Pembrolizumab	NCT04171219	Solid neoplasm	Phase II
Biogenesis	DPP8, DPP9, and FAP inhibitor	Talabostat	Pembrolizumab	NCT03910660	Prostate cancer/neuroendocrine tumors/small cell carcinoma	Phase I/II
	IL6	Tocilizumab	Nivolumab, ipilimumab	NCT04258150	Pancreatic cancer	Phase II
	IL6	Tocilizumab	Nivolumab, ipilimumab	NCT03999749	Melanoma	Phase II
	STAT3	BBI-608 (napabucasin)	Pembrolizumab	NCT02851004	Colorectal cancer	Phase I/II
			Ipilimumab/nivolumab/pembrolizumab	NCT02467361	Cancers	Phase I/II
			Nivolumab	NCT04299880	Oncology	Phase I
			Nivolumab	NCT03047839	Colorectal cancer	Phase II
	IL1-beta	Canakinumb	Spartalizumab	NCT04028245	Renal cell carcinoma	Early phase I
			Spartalizumab	NCT03742349	Triple-negative breast cancer	Phase I
			Pembrolizumab	NCT03968419	Non-small cell lung cancer	Phase II
			Pembrolizumab	NCT03631199	Non-small cell lung cancer	Phase III
	RIP-1	GSK3145095	Pembrolizumab	NCT03681951	Advenced solid tumors	Phase II
Recruitment	LXR-alpha/beta	RGX-104	Nivolumab, ipilimumab, pembrolizumab	NCT02922764	Malignant neoplasms	Phase I
	CXCR4/CXCL12	BL-8040/BKT140	Pembrolizumab	NCT02907099	Metatstatic pancreatic adenocarcinoma	Phase II
		BL-8040/BKT140	Pembrolizumab	NCT02826486	Metatstatic pancreatic denocarcinoma	Phase II
		AMD3100/plerixafor	Pembrolizumab	NCT04058145	Metastatic head and neck squamous cell carcinoma	Phase II
		X4P-001	Pembrolizumab	NCT02823405	Advenced melanoma	Phase I
		X4P-001	Nivolumab	NCT02923531	Clear cell renal cell carcinoma	Phase Ib/II
	CXCR4/CXCR7	NOX-A12/olaptesed	Pembrolizumab	NCT03168139	Metastatic colorectal cancer/metastatic pancreatic cancer	Phase Ib/II
	CXCR1/2	SX-682	Pembrolizumab	NCT03161431	Advenced melanoma	Phase I
	CXCR1/2	Navarixin	Pembrolizumab	NCT03473925	Non-small cell lung cancer/castration-resistant prostate cancer/MSS colorectal cancer	Phase II
	IL8	BMS-986253	Nivolumab	NCT04123379	Non-small cell lung cancer and HNCC	Phase II
	CCR2/5	BMS-813160	Nivolumab	NCT03184870	Metastatic colorectal cancer and pancreatic cancer	Phase I/II
	CCR2/5	BMS-813160	Nivolumab	NCT04123379	Non-small cell lung cancer and HNCC	Phase II
	CCR5	vicriviroc	Pembrolizumab	NCT03631407	Advenced MSS colorectal cancer	Phase II
	C5aR	IPH5401	Durvalumab	NCT03665129	Non-small cell lung cancer/hepatocellular carcinoma	Phase I
PI3K inhibitors	PI3K alpha	Duvelisib	Pembrolizumab	NCT04193293	Head and neck small cell cancer	Phase I/II
	PI3K-beta	GSK2636771	Pembrolizumab	NCT03131908	Melanoma	Phase I/II
	PI3K alpha, beta, gamma, delta	Copanlisib/BAY80−6946/aliqopa	Nivolumab	NCT03502733	Solid tumor and lymphoma	Phase I
			Nivolumab	NCT03711058	MSS proficient solid tumors	Phase I/II
			Nivolumab	NCT03735628	Non-small cell lung cancer/head and neck small cell cancer/colorectal cancer/hepatocellular carcinoma	Phase I/II
			Durvalumab	NCT03842228	Solid tumors	Phase I
			Nivolumab±ipilimumab	NCT04317105	Solid tumors	Phase I/II
	PI3K delta/gamma and low affinity alpha/beta	Idelalisib / GS-1101/zydelig	Pembrolizumab	NCT03257722	Non-small cell lung cancer	Phase I/II
	PI3K-delta	Itacitinib / INCB050465/IBI376	Pembrolizumab	NCT02646748	Advanced solid tumors	Phase I
Immunosuppressive functions and inhibitory signaling	ARG1	INCB001158	Pembrolizumab	NCT02903914	Metastatic solidd tumors	Phase I/II
		INCB001158	Pembrolizumab	NCT03361228	Solid tumors	Phase I/II
		Pegzilarginase	Pembrolizumab	NCT03371979	Small cell lung cancer	Phase I/II
	COX2	Celecoxib	Nivolumab	NCT03864575	‘Cold’ solid tumors	Phase I/II
	COX2	Celecoxib	Nivolumab+Ipilimumab	NCT03728179	Solid tumors	Phase I/II
	PGE2-receptor	Grapiprant/ARY-007	Pembrolizumab	NCT03696212	Non-small cell lung cancer	Phase I
	PGE2-receptor	Grapiprant/ARY-007	Pembrolizumab	NCT03658772	MSS colorectal cancer	Phase I
	NOS	L-NMMA	Pembrolizumab	NCT03236935	Non-small cell lung cancer/head and neck small cell cancer/classical Hodgkin's lymphoma/urothelial carcinoma/bladder DNA repair-deficiency disorders	Phase I
	NOS	L-NMMA	Pembrolizumab	NCT04095689	Triple-negative breast cancer	Phase II
	CD47	ALX148	Pembrolizumab	NCT03013218	Metastatic cancer/solid tumor/advanced cancer/non-Hodgkin's lymphoma	Phase I
	SIRPa	TTI-621	Pembrolizumab	NCT02890368	Melanoma, Merkel-cell carcinoma/squamous cell carcinoma/breast carcinoma/HPV-related malignant neoplasm/soft tissue sarcoma	Phase I
		TTI-621	Nivolumab	NCT02663518	Haematologic/solid tumor	Phase I
		TJ011133/TJC4	Pembrolizumab	NCT03934814	Solid tumors/lymphoma	Phase I
	ILT4	MK-4830	Pembrolizumab	NCT04165083	Advenced solid tumors	Phase I

FAP, fibroblast activation protein; HNCC, head and neck cancer; MSS, microsatellite intability; PI3K, phosphatidylinositol-3-kinase.