Emerging therapeutic frontiers in cancer: insights into posttranslational modifications of PD-1/PD-L1 and regulatory pathways

Wang, Rong; He, Shiwei; Long, Jun; Wang, Yian; Jiang, Xianjie; Chen, Mingfen; Wang, Jie

doi:10.1186/s40164-024-00515-5

Table 1 Targeting posttranslational modifications of PD-1/PD-L1

From: Emerging therapeutic frontiers in cancer: insights into posttranslational modifications of PD-1/PD-L1 and regulatory pathways

Target	Posttranslational modifications	Regulator	Therapy	Preclinical tumor model	Ref. No
PD-L1 S176,T180,S184	Serine/Threonine phosphorylation	GSK3β	Gefitinib + anti-PD-1	TNBC	[27]
PD-L1 S176,T180,S184	Serine/Threonine phosphorylation	GSK3β	Olaparib + anti–PD-1	TNBC	[27]
PD-L1 S195	Serine/Threonine phosphorylation	AMPK	Metformin + anti–CTLA4, D-mannose	BC, TNBC	[28, 155]
PD-L1 T210	Serine/Threonine phosphorylation	LRRK2	Vitamin B12	PDAC	[20]
PD-L1	Tyrosine phosphorylation	EGF	\	CSCC	[32]
PD-L1	Mono/Multiubiquitination	EGF	Gefitinib + SCH772984, PYR-41	CSCC	[33]
PD-L1	Poly-ubiquitination	β-TrCP	Resveratrol	TNBC	[27]
PD-L1	Poly-ubiquitination	Cullin3-SPOP	Palbociclib + anti–PD-1	BC, Colon cancer, CxCa	[35]
PD-L1	Poly- ubiquitination	STUB1	CMTM6 knockout, H1A	Melanoma	[45,46,47]
PD-L1	Ubiquitination	Casp8	\	Melanoma	[43, 44]
PD-L1	Ubiquitination	\	IFIT1	CRC	[36]
PD-L1	Poly- ubiquitination	SPOP	RIG-I knockout	CRC	[37]
PD-L1	Ubiquitination	RNF125	\	OSCC	[38]
PD-L1 K281	Poly- ubiquitination	HUWE1	PTPR + αCTLA-4	BC	[39]
PD-L1	Ubiquitination	VPRBP	USP2 knockout	Osteosarcoma	[40]
PD-L1	Ubiquitination	\	DHA	NSCLC, HCC	[41]
PD-L1	Poly- ubiquitination	Cullin3-SPOP	Canagliflozin	NSCLC	[48]
PD-L1	Ubiquitination	MIB2	\	Melanoma, CRC, NSCLC	[49]
PD-L1	Ubiquitination	\	PROTAC (21a, P22, AbTAC, CDTAC, ROTAC)	CRC, HCC, BC, NSCLC, bladder cancer, melanoma	[156,157,158,159,160,161,162]
PD-L1	Deubiquitination	CSN5	Curcumin + anti-CTLA4, PDIA6	TNBC, colon cancer, melanoma	[73,74,75]
PD-L1 K6, K11, K27, K29, K33	Deubiquitination	USP22	USP22 inhibitor: Rottlerin and Morusin	HCC, NSCLC	[76, 77]
PD-L1	Deubiquitination	USP9X	\	OSCC	[78]
PD-L1	Deubiquitination	UCHL1	\	NSCLC	[83]
PD-L1	Deubiquitination	OTUB1	\	BC	[84]
PD-L1 K270	Deubiquitination	USP2	USP2 knockout, USP2 inhibitor	CRC, PC	[79]
PD-L1	Deubiquitination	USP51	DHM	NSCLC	[80]
PD-L1	Deubiquitination	USP8	USP8 inhibitor + anti–PD-L1	PCA	[81]
PD-L1	Deubiquitination	USP7	A11 + PD-L1 mAb	BC, NSCLC, melanoma	[82]
PD-L1	Deubiquitination	USP20	\	BC	[85]
PD-L1	Deubiquitination	USP18	\	Bladder cancer	[86]
PD-L1 N192,N200	N-linked glycosylation	B3GNT3	STM108,Gefitinib	TNBC	[90]
PD-L1	N-linked glycosylation	Sigma1	IPAG	TNBC, PC	[91]
PD-L1	N-linked glycosylation	FKBP51 s	SAFit	GBM	[92]
PD-L1	N-linked glycosylation	GLT1D1	\	BCL	[93]
PD-L1	N-linked glycosylation	SLC35C1	\	LUAD	[94]
PD-L1	N-linked glycosylation	B4GALT1	\	LUAD	[95]
PD-L1	N-linked glycosylation	STT3	Etoposide + anti-Tim-3	BC, NPC, CxCa	[39, 96,97,98,99]
PD-L1	N-linked glycosylation	\	α-mangostin	TNBC	[188]
PD-L1	N-linked glycosylation	SEC61G	\	GBM	[100]
PD-L1	N-linked glycosylation	MCT4	\	TNBC	[101]
PD-L1	O-linked glycosylation	GALNT2/14	\	LUAD	[105]
PD-L1	O-linked glycosylation	GFAT1	\	Lung cancer	[106]
PD-L1	Ectodomain shedding	MMP9, 13	\	Mesenchymal stromal cells	[64]
PD-L1	Ectodomain shedding	MMP7, 13	CL82198, Paclitaxel	HNSCC	[65]
PD-L1	Ectodomain shedding	MMP2, 9, 13	HE4	OC	[66]
PD-L1	Disulfide bond formation	PDIA5	\	HCC, GBM, PC	[109]
PD-L1	Disulfide bond formation	ERO1-α	ERO1-α knockout	TNBC	[108]
PD-L1	S-palmitoylation	PPT1	PPT1 inhibitor	Melanoma, HCC	[190, 191]
PD-L1 C272	S-palmitoylation	ZDHHC9	2-BP	BC, Lung cancer	[112,113,114,115]
PD-L1 C272	S-palmitoylation	ZDHHC3	CPP-S1,2-BP, SP-PROTAC	CRC	[116, 196]
PD-L1	S-palmitoylation	FASN	DHA	Bladder cancer	[41, 117]
PD-L1	S-palmitoylation	DHHC5	DHA	PCA	[41]
PD-L1	ADP-Ribosylation	ARF6	\	PCA	[119, 120]
PD-L1	Acetylation	EGF	\	CSCC	[33]
PD-L1 K263	Acetylation	p300, HDAC2	HDAC2 inhibitor	TNBC	[125]
PD-L1	Acetylation	VPA	\	PCA	[126]
PD-L1	Autophagic degradation	ING4	CK2 inhibitor	NSCLC	[161]
PD-L1	SUMOylation	TRIM28	\	GC	[88]
PD-L1	ISGylation	ISG15	\	LUAD	[57]
PD-L1	UFMylation	UFL1, UFM1	UFSP2 inhibitor	TNBC, HCC	[58]
PD-L1 K162	Methylation	SETD7	\	NSCLC	[22]
PD-1 Y223,Y248	Tyrosine phosphorylation	Lck	Shp2	BL	[133]
PD-1 K48	Poly-ubiquitination	FBXO38	IL-2, CISH knockout	CRC, NSCLC	[13, 136]
PD-1	Ubiquitination	c-Cbl	\	CRC	[137]
PD-1 K48	Poly-ubiquitination	FBW7	Oridonin	NSCLC	[12]
PD-1	Ubiquitination	MDM2	\	Colon cancer	[138]
PD-1 N49,N74	N-linked glycosylation	Fut8	2 F-Fuc	Melanoma	[140]
PD-1	S-palmitoylation	DHHC9	\	CRC	[141]

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ISSN: 2162-3619

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