Table 1.
Phagocytosis checkpoints expression and working mechanisms in various diseases
| Checkpoint | Disease | Expression and mechanisms | Reference |
|---|---|---|---|
| CD47 | diffuse large B-cell lymphoma | highly expressed, immune evasion via CD47-SIRPα axis | 391 |
| CD47 | chronic lymphocytic leukemia | overexpressed, targeting CD47 promotes apoptosis | 392 |
| CD47 | Burkitt lymphoma | overexpressed | 263,393 |
| CD47 | primary effusion lymphoma | highly expressed, promotes phagocytosis | 394 |
| CD47 | T-cell lymphoma | variably expressed. CD47 promotes TCL metastasis by up-regulating AKAP13-mediated RhoA activation | 395,396 |
| CD47 | acute myeloid leukemia | highly expressed, increase leukemia stem cells | 397 |
| CD47 | myelodysplastic syndrome | The higher CD47 indicates poor prognosis in MDS patients. | 398 |
| CD47 | multiple myeloma | High CD47 expression in MM patients is related to p53 deletions and elevated β-2 macroglobulin levels. | 399,400 |
| CD47 | SCLC | highly expressed | 401 |
| CD47 | NSCLC | decreasing neutrophil apoptosis and phagocytosis in NSCLC | 253 |
| CD47 | glioblastoma | GBM cells with higher CD47 expression possess the characteristics of stem cells and have poor clinical results | 402 |
| CD47 | breast cancer | Highly expressed CD47 promotes CSC resistance. | 403 |
| CD47 | ovarian cancer | CD47 inhibits macrophage phagocytosis and promotes cell growth and metastasis in EAOC. | 404 |
| CD47 | hepatocellular carcinoma | Macrophages induce CD47 upregulation in HCC patients by IL-6 and correlate with poor survival. | 46 |
| CD47 | cholangiocarcinoma | Blocking CD47-SIRPα pathway increases phagocytosis of macrophages and inhibits CCA growth and metastasis. | 405 |
| CD47 | pulmonary arterial hypertension | The activation of CD47 by TSP-1 promotes hypoxic PAH and the activated CD47 inhibits the upregulation of Cav-1 and promotes ROS in PAH. | 269 |
| CD47 | systemic lupus erythematosus | CD47 has been demonstrated to potentiate the inflammatory response in SLE patients. | 406,407 |
| CD47 | acute kidney injury | The activated CD47 promotes AKI by limiting autophagy. | 270–272,408 |
| CD47 | Ischemia-reperfusion injury | under hypoxia and following IR, TSP-1/CD47 axis is induced in renal tubular epithelial cells (RTEC). | 271 |
| CD47 | cerebral malaria | The lymphocytes increased in CD47-blocked mice, and the IL22, TNF-α, and IFN-γ were increased in the circulation. | 409 |
| CD47 | fibrosis | Targeting CD47 attenuates fibrosis induced by various diseases. | 410 |
| CD47 | COVID-19 pathogenesis | CD47 mediates the immune escape in infectious diseases caused by parasites, bacteria, and viruses. | 411,412 |
| CD47 | colon cancer | Inhibition of CD47 reduced the migration of SW480 cells. | 413,414 |
| CD47 | autoimmune uveitis | CD47 regulates the SIRPα+ on DCs, which is crucial to the induction in EAU. | 415 |
| CD47 | uveal melanoma | Patients with higher CD47 have higher CD4+ and CD8+ T cells. | 283 |
| CD47 | thyroid cancer | CD47 involves the up-regulation of the PD-1 oncogenic signaling | 416 |
| CD47 | type1 diabetes | CD47-SIRPα deficiency or interruption leads to the upregulation of lymphocyte activation, β-cell destruction and cytotoxicity. | 417 |
| CD47 | age-related macular degeneration | Pharmacological activation of CD47 induces the resolution of subretinal chronic inflammation that leads to irreversible blindness in AMD. | 418 |
| CD47 | isoproterenol (ISO)-induced cardiac hypertrophy | Blocking CD47 inhibits isoproterenol-induced cardiac hypertrophy via autophagy | 419,420 |
| CD47 | atherosclerosis | CD47-inhibition restores phagocytosis and prevents atherosclerosis | 421 |
| CD47 | pancreatic cancer | The restoration of miR-340 reduces CD47 and facilitates phagocytosis, suppressing tumor progression | 422 |
| PD-L1 | autoimmune diabetes | In pancreatic beta cells in NOD mice, the increase of PD-L1 suppressed disease progression | 423 |
| PD-L1 | inflammatory bowel disease | PD-L1 was expressed highly in intestinal epithelial cells of inflammatory bowel disease (IBD) patients | 424 |
| PD-L1 | allergic asthma | Upregulation of PD-L1 downregulates AHR and inflammation. | 46,282 |
| PD-L1 | multiple sclerosis | Increased PD-L1 expression inhibits proinflammatory response. | 425,426 |
| PD-L1 | rheumatoid arthritis | Upregulation of PD-L1 inhibits proinflammatory response. | 280,281 |
| PD-L1 | psoriatic | Upregulation of PD-L1 on T-MSCs inhibits and decreases immune response. | 427 |
| PD-L1 | atherosclerotic plaque | PD-1/PD-L1 pathway downregulates the proatherogenic T cell response and atherosclerosis. | 428–430 |
| PD-L1 | renal cell carcinoma | High levels of PD-L1 expression show a worse prognosis. | 431,432 |
| PD-L1 | HCC cancer | Increased expression of PD-L1 was associated with a significantly poorer prognosis. | 433 |
| PD-L1 | NSCLC | Expression of PD-L1 indicates a worse prognosis. | 434,435 |
| PD-L1 | melanoma cancer | PD-L1 correlates with worse patients survival. | 436,437 |
| PD-L1 | breast cancer | PD-L1 relates to tumor size and a lower survival rate | 438 |
| PD-L1 | ovarian cancer | PD-L1-high patients have a poor prognosis | 439 |
| PD-L1 | pancreatic cancer | PD-L1-high patients indicate a poorer prognosis than the PD-L1-low patients. | 440 |
| PD-L1 | cervical cancer | PD-L1 acts as a prognostic factor of poor survival. | 441 |
| PD-L1 | colon cancer | PD-L1 is upregulated and correlates to poor prognosis. | 442,443 |
| PD-L1 | esophageal cancer | PD-L1 is highly expressed and indicates poorer survival. | 444 |
| PD-L1 | large B-cell lymphoma | PD-L1 positive DLBCL patients had a shorter survival rate than those PD-L1 negative patients. | 445 |
| PD-L1 | glioblastoma | PD-L1 high expression correlates to shorter overall survival. | 446 |
| PD-L1 | prostate cancer | PD-L1 was highly expressed in high-risk patients. PD-L1 positivity relates to independent unfavorable prognostic. | 447,448 |
| PD-L1 | gastric cancer | High PD-L1 indicates a shorter survival time. | 449 |
| GD2 | neuroblastoma | Progression-free survival (PFS) was inversely related to circulating GD2 levels | 450 |
| GD2 | SCLC | GD2 is expressed in SCLC lines and GD2 expression is also much higher in SCLC cell lines than in normal lung cell lines | 324,325 |
| GD2 | osteosarcoma | GD2 is highly expressed in osteosarcoma cells. | 319,320 |
| GD2 | ewing sarcoma | The expression of GD2 is a characteristic of Ewing sarcomas. It is a target antigen for immunotherapy. | 451 |
| GD2 | soft tissue sarcoma | A large percentage of soft tissue sarcoma patients express GD2. | 452 |
| GD2 | gliomas | GD2 is a commonly expressed surface antigen of gliomas. | 453 |
| GD2 | Melanoma | Melanoma cells contain abundant amounts of GD2. | 326,327 |
| CD22 | leukemia | CD22 is highly positive in various proportions in leukemia. | 454 |
| CD22 | B-cell lymphoma | CD22 is expressed in non-Hodgkin’s lymphoma, DLBL, and small lymphocytic lymphoma. | 147–149 |
| STC-1 | gastric cancer | STC-1 was upregulated in gastric cancer, and higher expression of STC-1 related to survival rate. STC-1 is a potential blood marker for predicting biological tumor aggressiveness. | 304,305,307 |
| STC-1 | colorectal cancer | STC-1 was higher in the cancer tissue and indicated a poor prognosis. | 455 |
| STC-1 | ovarian cancer | STC-1 expression was upregulated in ovarian cancer patients and it correlated with ovarian cancer patients’ overall survival. | 306,456 |
| STC-1 | breast cancer | STC-1 expression is upregulated and is correlated with poor prognosis. | 457 |
| STC-1 | bladder cancer | The expression of STC-1 was upregulated in a higher stage bladder cancer and the high expression of STC-1 predicts a poor prognosis in bladder cancer. | 300,458 |
| STC-1 | glioblastoma | The STC-1 expression is increased in glioblastoma tissues, and STC-1 revealed a significant association with poor outcomes in patients. | 301 |
| STC-1 | acute leukemia | High STC-1 gene expression is associated with shorter overall survival in acute leukemia. | 302 |
| STC-1 | hepatocellular carcinoma | Higher serum STC-1 level in HCC patients was correlated with poorer survival. | 459 |
| STC-1 | neuroinflammation | STC-1 overexpression reduces brain injury, | 313 |
| STC-1 | diabetic nephropathy | STC-1 improves renal injury in diabetic nephropathy. Patients with high levels of STC-1 have a better prognosis. | 118 |
| STC-1 | asthma | Serum STC-1 is decreased in asthma. STC-1 reduces airway hyperresponsiveness (AHR) and inflammation. | 314 |
| STC-1 | lung injury | STC-1 protects against oxidant-induced lung injury. | 312 |
| STC-1 | nonalcoholic fatty liver | Suppressed STC-1 expression stimulates the occurrence of nonalcoholic fatty liver. | 316 |
| MHC-I (HLA-B27) | ankylosing spondylitis | HLA-B27 is thought to be important in the pathogenesis of ankylosing spondylitis, contributing approximately 20.1% to the heritability of ankylosing spondylitis, associated with the presentation of non-standard antigenic peptides. | 291 |
| MHC-I (HLA-B27) | Lyttle’s syndrome | Reiter’s syndrome is an HLA-B27-associated disease. | 397 |
| MHC-I (HLA-B27) | acute anterior uveitis | HLA-B27-associated immune response promotes the development of acute anterior uveitis. | 460 |
| MHC-I (HLA-B27) | juvenile rheumatoid arthritis | About 10% of juvenile chronic arthritis patients carry HLA-B27. | 461 |
| MHC-I | celiac disease | Different HLA alleles play opposite roles in celiac disease. | 462 |
| MHC-I | Graves’ disease | Patients carrying HLA-A10 and HLA-B8 Graves’ disease tend to develop the disease at an earlier age. | 463 |
| MHC-I | juvenile diabetes mellitus | Different subtypes of HLA affect juvenile diabetes mellitus onset and progression. | 464 |
| MHC-I | melanoma | Tumor escapes through MHC expression deficiency. | 465 |
| MHC-I | Laryngeal carcinomas; colorectal carcinomas; bladder carcinomas | HLA haplotype loss in laryngeal cancer is associated with loss of heterozygosity in the chromosome 6p21 region | 466 |
| MHC-I | head and neck squamous cell carcinoma | Lower expression of HLA is related to the survival and recurrence of HNSCC. | 467 |
| MHC-I | breast carcinoma | The loss of heterozygosity on a chromosome 6 (the HLA-I region of chromosome) and 15 (the β2-microglobulin (β2M) region) is highly prevalent in breast cancer. | 468 |
| MHC-I | neuroblastoma | MHCI expression relates to neuroblastoma stage and prognosis. | 469 |
| MHC-I | colorectal liver metastases | High expression of MHCI with significantly increased overall survival. | 470 |
| MHC-I | ovarian cancer | HLA-A02 serves as a prognostic biomarker. | 471 |
| MHC-I | non-small-cell lung cancer | Reduced HLA expression did not affect prognosis, but the heterogeneous expression of HLA had a poor prognosis. | 472 |
| CD24 | autoimmune disease | CD24 has co-stimulatory activity and furthermore, CD24 is a genetic checkpoint for balanced T cell proliferation. | 473 |
| CD24 | inflammation | CD24 relates to various DAMPs, including nucleolin, heat-shock protein and high mobility histone box protein 1. | 87 |
| CD24 | GvHD | The CD24-Siglec-G/10 selectively modulates the host response to DAMPs and regulates the immune response. | 87 |
| CD24 | bacterial and viral infections, sepsis, COVID-19 | CD24 acts as an important immune regulator in complex physiological diseases characterized by excessive inflammation | 474 |
| CD24 | multiple sclerosis | Individuals with the CD24V/V genotype have a greater susceptibility to and progression of MS than individuals with the CD24A/V and CD24A/A genotypes. | 475 |
| CD24 | Breast cancer | CD24(+) cells are responsible for breast tumor heterogeneity. | 476 |
| CD24 | colorectal cancer | CD24-dependent activation of the MAPK pathway promotes colorectal cancer cell proliferation in vitro and in vivo. | 477 |
| CD24 | lung adenocarcinoma, ovarian carcinoma, glioblastoma | CD24 inhibits tissue factor pathway inhibitor-2 (TFPI-2), which in turn promotes tumor cell invasion in a c-Src-dependent manner. | 478 |
| CD24 | osteosarcoma, prostate cancer, | CD24 promotes the infiltration and metastasis of various tumors by HIF1, EPCaM | 479 |
| CD24 | cervical cancer | CD24 is upregulated in cervical cancer tissues and inhibits apoptosis by affecting the MAPK signaling pathway in cervical cancer. | 480 |
| CD24 | hepatocellular carcinoma | High CD24 is associated with poor prognostic markers, and overexpression of CD24 is associated with high proliferation and metastasis. | 481 |
| CD24 | Prostate cancer | CD24 is significantly increased in contrast to prostate hyperplasia. | 482 |
| CD24 | Ovarian Cancer | CD24 expresses not only in the cell membrane but also intracellularly, appearing in exosomes. | 373 |