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. 2022 Sep 16;13:1027838. doi: 10.3389/fimmu.2022.1027838

Table 1.

The characteristics of 20 immune checkpoint-related genes.

Gene Names Protein Names Subcellular Location Normal Tissue Specificity Cancer Types Function References
SIGLEC15 sialic acid-binding Ig-like lectin 15 plasma membrane macrophage and/or dendritic cells of spleen and lymph nodes lymphoma, leukemia, thyroid cancer, and renal cell cancer TAM-associated Siglec-15 has a potent immune suppressive effect on T-cell responses (23, 24)
VTCN1 V-set domain-containing T-cell activation inhibitor 1 plasma membrane activated T- and B-cells, monocytes, and dendritic cells breast cancer, ovarian cancer, and renal cell cancer negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity (25, 26)
HHLA2 human endogenous retrovirus-H long terminal repeat-associating protein 2 plasma membrane colon, kidney, testis, B-cells, and dendritic cells colorectal cancer, pancreatic cancer, and gastric cancer inhibits CD8+ T and NK cell function and killing (27, 28)
FGL2 fibroleukin extracellular region and exosome cytotoxic T-cells leukemia and lymphoma induces CD8 + T cell apoptosis to limit T cell immunity through the inhibitory Fc receptor FcγRIIB (29, 30)
ENTPD1 ectonucleoside triphosphate diphosphohydrolase 1 (CD39) plasma membrane activated lymphoid cells and endothelial tissues glioma, gastric cancer, and renal cell cancer hydrolyzes eATP and eADP into eAMP to provide raw materials for CD73 (31, 32)
PVR poliovirus receptor (CD155) cytoplasm, cell surface and extracellular space widely expressed esophageal carcinoma, adrenocortical carcinoma, and colon carcinoma provides tumors with a mechanism of immunoevasion from NK cells (33, 34)
CD24 signal transducer CD24 cell surface B-cells Breast cancer, colorectal cancer, and gastric cancer regulates the proliferation of B-cells and prevents their terminal differentiation into antibody-forming cells (35, 36)
CD200 OX-2 membrane glycoprotein cell membrane widely expressed pheochromocytoma, paraganglioma and renal cell cancer inhibits T-cell proliferation (37, 38)
TNFRSF14 tumor necrosis factor receptor superfamily member 14 (CD270) cell membrane lung, spleen, and thymus melanoma, lymphoma, and lung cancer synergistically inhibits the function of lymphocytes with BTLA (39, 40)
LGALS9C galectin-9C cytosol and nucleus widely expressed head and neck squamous cell carcinoma, and colorectal cancer interacts with multiple molecules to regulate immune cells proliferation and death (41, 42)
NT5E 5’-nucleotidase (CD73) cell membrane activated lymphoid cells and endothelial tissues thyroid cancer, gastric cancer, sarcoma, and glioma hydrolyzes eAMP into immunosuppressive adenosine (43, 44)
LAG3 lymphocyte activation gene 3 protein (CD223) cell membrane and extracellular region activated T-cells and NK cells leukemia and testicular germ cell tumors negatively regulates the proliferation, activation, effector function and homeostasis of both CD8+ and CD4+ T-cells (45, 46)
TIGIT T-cell immunoreceptor with immunoglobulin and ITIM domains cell membrane T-cells and NK cells leukemia and lung adenocarcinoma suppresses T-cell activation by promoting the generation of mature immunoregulatory dendritic cells (47, 48)
C10orf54 V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA) cell membrane placenta, spleen, plasma blood leukocytes, and lung leukemia and pancreatic cancer immunoregulatory receptor which inhibits the T-cell response (49, 50)
BTLA B- and T-lymphocyte attenuator (CD272) cell membrane lymph node lymphoma and leukemia inhibitory receptor on lymphocytes that negatively regulates antigen receptor signaling (51, 52)
PDCD1 programmed cell death protein 1 (PD-1) cell membrane induced at programmed cell death lymphoma, melanoma, and lung cancer plays a critical role in induction and maintenance of immune tolerance (53, 54)
CD276 CD276 antigen cell membrane peripheral blood lymphocytes or granulocytes sarcoma, glioma, lung cancer, and prostate cancer inhibits T-cell-mediated immune response and NK cell-mediated lysis (55, 56)
CTLA4 cytotoxic T-lymphocyte protein 4 cell membrane, Golgi apparatus, cytoplasm widely expressed lymphoma, leukemia melanoma, and lung cancer inhibitory receptor acting as a major negative regulator of T-cell responses (57, 58)
CD274 programmed cell death 1 ligand 1 (PD-L1) cell membrane, nucleoplasm, and extracellular exosome lung, heart, placenta, and kidney lymphoma, melanoma, and lung cancer as a ligand for the inhibitory receptor PD-1, modulates the activation threshold of T-cells and limits T-cell effector response (53, 54)
CD47 leukocyte surface antigen CD47 cell surface and extracellular exosome widely expressed leukemia, ovarian cancer, lung cancer, and pancreatic cancer prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells (59, 60)

TAM, tumor-associated macrophage; NK, natural killer cell; eAMP, extracellular adenosine monophosphate; eADP, extracellular adenosine diphosphate; eATP, extracellular adenosine triphosphate; ITIM, immunoreceptor tyrosine-based inhibitory motif.