Table 3.

Potential drugs intervening PD-L1 and CTLA-4

Drugs		Mechanism	PD-L1 or CTLA-4	Cancer types	References
PD-L1	metformin	phosphorylating oncogene YAP1	Downregulation	CRC	[243]
	MS NPs		Downregulation	breast cancer	[244]
	PARPi	inactivating GSK3β	Upregulation	breast cancer	[245]
	TMZ		Upregulation	GBM	[246]
	actinomycin D		Downregulation	GBM	[246]
	Pemetrexed and sildenafil		Downregulation	NSCLC	[247]
	AR42 and valproate	inhibiting histone deacetylase	Downregulation	NSCLC	[247]
	DSF/Cu2+	inactivating PARP1 and phosphorylating GSK3βat Ser9	Upregulation	HCC	[248]
	ipatasertib, capivasertib, uprosertib, and MK-2206	inhibiting Akt	Downregulation	breast cancer	[249]
	DS-8201a	targeting HER2	Upregulation	breast cancer	[250]
	Verteporfin	inhibiting STAT1-IRF1-TRIM28 signaling cascade	Downregulation	T-cell leukemia, B-cell leukemia, ovarian, osteoblastoma, and NSCLC	[251]
	LY294002	inhibiting PI3K	Downregulation	gastric cancer	[61]
	cetuximab, erlotinib, and selumetinib	inhibiting MAPK signaling	Downregulation	LUAD	[57]
	trametinib	inhibiting MAPK signaling	Upregulation	breast cancer	[56]
	Belinostat	inducing IFN-γ	Upregulation	HCC	[252]
	C108	Inhibiting G3BP2	Downregulation	GBM	[139]
	Pembrolizumab	inhibiting interaction of PD-L1 with PD-1		urothelial cancer, melanoma, HNSCC, and NSCLC	[253]
	Nivolumab and Atezolizumab	inhibiting interaction of PD-L1 with PD-1		NSCLC, urothelial cancer, RCC, and melanoma	[253]
	Durvalumab and Avelumab	inhibiting interaction of PD-L1 with PD-1		urothelial cancer	[253]
	Envafolimab	inhibiting interaction of PD-L1 with PD-1		prostate cancer, NSCLC, breast cancer, gastrointestinal cancer, melanoma, cervical cancer, HNSCC, bladder cancer, cholangiocarcinoma	[254]
	MDX-1105 and CS-1001	inhibiting interaction of PD-L1 with PD-1		NSCLC, melanoma, RCC	[9]
	CK-301	inhibiting interaction of PD-L1 with PD-1		NSCLC, HNSCC, melanoma, RCC, urothelial cancer, Hodgkin’s lymphoma	[254]
	TQB-2450	inhibiting interaction of PD-L1 with PD-1		melanoma	[254]
	BGB-A333	inhibiting interaction of PD-L1 with PD-1		advanced solid tumor	[254]
CTLA-4	Ipilimumab	inhibiting interaction of CTLA-4 with B7		RCC, prostate cancer, cervical cancer, CRC, NSCLC, gastric cancer, pancreatic cancer, ovarian cancer, urothelial cancer, and melanoma	[255]
	Tremelimumab	inhibiting interaction of CTLA-4 with B7		HCC	[256]
	p344	inhibiting interaction of CTLA-4 with B7			[257]
	SAHA		Downregulation		[258]
	CKD-L		Upregulation		[259]