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] |
Olaparib + anti–PD-1 | |||||
PD-L1 S195 | Serine/Threonine phosphorylation | AMPK | Metformin + anti–CTLA4, D-mannose | BC, TNBC | |
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 | |
PD-L1 | Ubiquitination | Casp8 | \ | Melanoma | |
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 | |
PD-L1 | Deubiquitination | CSN5 | Curcumin + anti-CTLA4, PDIA6 | TNBC, colon cancer, melanoma | |
PD-L1 K6, K11, K27, K29, K33 | Deubiquitination | USP22 | USP22 inhibitor: Rottlerin and Morusin | HCC, NSCLC | |
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 | |
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 | |
PD-L1 C272 | S-palmitoylation | ZDHHC9 | 2-BP | BC, Lung cancer | |
PD-L1 C272 | S-palmitoylation | ZDHHC3 | CPP-S1,2-BP, SP-PROTAC | CRC | |
PD-L1 | S-palmitoylation | FASN | DHA | Bladder cancer | |
PD-L1 | S-palmitoylation | DHHC5 | DHA | PCA | [41] |
PD-L1 | ADP-Ribosylation | ARF6 | \ | PCA | |
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 | |
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 | 2Â F-Fuc | Melanoma | [140] |
PD-1 | S-palmitoylation | DHHC9 | \ | CRC | [141] |