Table 1 The mechanisms of PD-L1 regulation in the tumor microenvironment

Genomic alterations

Gene amplification or translocation

Up

Classical Hodgkin lymphoma;

Small-cell lung cancer;

Large B-cell lymphoma

[23,24,25]

Epigenetic regulation

H3K4me3

Up

Pancreatic cancer

[27]

H3K27me3

Down

Hepatocellular carcinoma

[29]

Methylation of some CpG loci in CD274 promoter

Down

Melanoma;

Head and neck squamous cell carcinomas;

Colorectal cancer

[33,34,35]

Histone acetylation

Up

Drug-resistant cancer cells;

[39]

Transcriptional regulation

IFN-α, IFN-β, IFN-γ

Up

Melanoma;

Hepatocellular carcinoma;

Gastric carcinoma

[44, 46, 48]

IL-6

Up

Prostate cancer;

Hepatocellular carcinoma;

Glioblastoma;

Non-small cell lung cancer

[50,51,52,53]

TNF-α

Up

Prostate cancer;

Colon cancer;

Renal cell carcinoma

[54, 55]

IL-10

Up

Oral squamous cell carcinoma

[56]

IL-27

Up

Epithelial ovarian cancer;

Prostate cancer;

Non-small cell lung cancer

[57]

TGF-β

Up

Lung cancer

[60, 61]

EGFR

Up

Lung cancer

[62]

MAPK

Up

Lung cancer;

Melanoma;

Pancreatic cancer;

Triple-negative breast cancer

[67,68,69,70]

PTEN

Down

Triple-negative breast cancer

[74]

PI3K

Up

Gastric cancer;

Her2-overexpressing cell lines;

Colorectal cancer;

Head and neck squamous cell carcinomas;

Non-small cell lung cancer

[75,76,77,78,79]

JAK-STAT

Up

Natural killer/T-cell lymphoma;

Non-small cell lung cancer;

Triple-negative breast cancer;

[80,81,82,83]

NF-κB

Up

Natural killer/T-cell lymphoma;

Gastric carcinoma;

Non-small cell lung cancer;

Triple-negative breast cancer

[84, 87,88,89,90]

HIF-1

Up

Prostate cancer;

Breast cancer;

Nasopharyngeal carcinoma

[92, 93]

Myc

Up

Leukemia and lymphomas;

Melanoma;

Non-small cell lung cancer;

Hepatocellular carcinoma;

Renal cell carcinoma;

Colorectal carcinoma;

Esophageal squamous cell carcinoma;

Pancreatic cancer

[96,97,98,99]

ALK

Up

Non-small cell lung cancer;

Anaplastic large cell lymphoma

[103, 104]

Met

Up

Non-small cell lung cancer

[107,108,109,110]

BRD4

Up

Ovarian cancer

[112]

DSB

Up

Osteosarcoma;

Non-small cell lung cancer;

Prostate cancer

[114]

Post-transcriptional regulation

miR-148a-3p

Down

Colorectal cancer

[116]

miR-873

Down

Breast cancer

[117]

miR-34a

Down

B-cell lymphoma;

Acute myeloid leukemia

[118, 126]

miR-200 family

Down

Non-small cell lung cancer;

Hepatocellular carcinoma

[119, 120]

miR-142-5p

Down

Pancreatic cancer

[121]

miR-424

Down

Ovarian cancer

[122]

miR-214

Down

Diffuse large B-cell lymphoma

[123]

miR-497-5p

Down

Clear cell renal cell carcinoma

[124]

miR-140

Down

Non-small cell lung cancer

[125]

miR-23a-3p/PTEN axis

Up

Liver Cancer

[127]

miR-200a/PTEN axis

Up

Osteosarcoma

[128]

miR-27a-3p/ MAGI2/PTEN axis

Up

Breast cancer

[129]

miR-145/c-Myc axis

Down

Ovarian cancer

[130]

miR-18a/ PTEN, WNK2, SOX6 axis

Up

Cervical cancer

[131]

miR-BART5/PIAS3/pSTAT3

Up

Gastric cancer

[133]

RAS-tristetraprolin

Up

RAS mutant cancer

[135]

Angiotensin II/human antigen R

Up

Non-small cell lung cancer

[136]

Post-translational modification

Ubiquitination

Down

Multiple cancers

[138, 141, 142]

Y112 phosphorylation

Up

Hepatocellular carcinoma

[143]

S195 phosphorylation

Down

Breast cancer

[144]

T180 and S184 phosphorylation

Down

Breast cancer

[145]

Glycosylation

Up

Breast cancer;

Glioma

[145, 149, 150]

Palmitoylation

Up

Breast cancer;

Colon cancer

[151, 152]