Interactions of natural killer cells in pancreatic cancer (WP5092)
Homo sapiens
This pathway shows the interaction between a Natural Killer cell and a pancreatic tumor cell. With the specific cell receptors found on the NK cell, it is able to recognize malignant cells and secrete cytokines and chemokines to create an enhanced immune response. Their ability to activate both innate- as well as adaptive immune cells makes the NK cell an excellent target for novel immunotherapy treatments against pancreatic cancer. The pathway curation is mainly based on a systemic review by Van Audenaerde et al. in 2018 (10.1016/j.pharmthera.2018.04.003).
Authors
Nanda Knoops , Martina Summer-Kutmon , Eric Weitz , and Egon WillighagenActivity
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Cited In
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Organisms
Homo sapiensCommunities
PancCanNetAnnotations
Cell Type Ontology
natural killer cell neoplastic cellDisease Ontology
pancreatic cancerPathway Ontology
pancreatic cancer pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| Glucose | Metabolite | chebi:17234 | |
| lactate | Metabolite | chebi:24996 | |
| CXCL8 | Metabolite | chebi:138181 | |
| NCR1 | GeneProduct | ensembl:ENSG00000189430 | |
| BMI1 | GeneProduct | ensembl:ENSG00000168283 | |
| NCR3 | GeneProduct | ensembl:ENSG00000204475 | |
| GATA2 | GeneProduct | ensembl:ENSG00000179348 | |
| NCR3LG1 | GeneProduct | ensembl:ENSG00000188211 | |
| ADAM17 | GeneProduct | ensembl:ENSG00000151694 | |
| ADAM10 | GeneProduct | ensembl:ENSG00000137845 | |
| MYC | GeneProduct | ensembl:ENSG00000136997 | |
| PVR | GeneProduct | ensembl:ENSG00000073008 | |
| IGHG1 | GeneProduct | ensembl:ENSG00000211896 | |
| KLRK1 | GeneProduct | ensembl:ENSG00000213809 | |
| CCL1 | GeneProduct | ensembl:ENSG00000108702 | |
| CCL4 | GeneProduct | ensembl:ENSG00000275302 | |
| CCL5 | GeneProduct | ensembl:ENSG00000271503 | |
| CCL3 | GeneProduct | ensembl:ENSG00000277632 | |
| TNF | GeneProduct | ensembl:ENSG00000232810 | TNFα |
| CCL2 | GeneProduct | ensembl:ENSG00000108691 | |
| FOXO1 | GeneProduct | ensembl:ENSG00000150907 | |
| IFNG | GeneProduct | ensembl:ENSG00000111537 | IFNγ |
| ULBP1 | Protein | uniprot:P16757 | UL16 |
| MICB | Protein | uniprot:F5H7Q8 | |
| GATA2 | Protein | uniprot:P23769 | |
| MICA | Protein | uniprot:A0A024RCL3 | |
| NCR3LG1 | Protein | uniprot:Q68D85 | B7H6 |
| PVR | Protein | uniprot:P15151 | CD155 |
| IGHG1 | Protein | uniprot:P01857 | |
| IgE | Protein | wikidata:Q79455 | |
| KLRK1 | Protein | uniprot:P26718 | NKG2-D |
| PRF1 | Protein | uniprot:P14222 | Perforin-1 |
| GZMB | Protein | uniprot:P10144 | Granzyme B |
| GM-CSF | Protein | uniprot:P04141 | |
| NCR3 | Protein | uniprot:O14931 | NKp30 |
| CD226 | Protein | uniprot:Q15762 | DNAM1 |
| CD96 | Protein | uniprot:P40200 | TACTILE |
| TIGIT | Protein | uniprot:Q495A1 | |
| NCR1 | Protein | uniprot:O76036 | NKp46 |
| FCGR3A | Protein | uniprot:P08637 | FcγRIII |
References
- The biology of human natural killer-cell subsets. Cooper MA, Fehniger TA, Caligiuri MA. Trends Immunol. 2001 Nov;22(11):633–40. PubMed Europe PMC Scholia
- Granzymes are essential for natural killer cell-mediated and perf-facilitated tumor control. Pardo J, Balkow S, Anel A, Simon MM. Eur J Immunol. 2002 Oct;32(10):2881–7. PubMed Europe PMC Scholia
- Immunoglobulin E antibodies from pancreatic cancer patients mediate antibody-dependent cell-mediated cytotoxicity against pancreatic cancer cells. Fu SL, Pierre J, Smith-Norowitz TA, Hagler M, Bowne W, Pincus MR, et al. Clin Exp Immunol. 2008 Sep;153(3):401–9. PubMed Europe PMC Scholia
- Perforin: structure, function, and role in human immunopathology. Voskoboinik I, Dunstone MA, Baran K, Whisstock JC, Trapani JA. Immunol Rev. 2010 May;235(1):35–54. PubMed Europe PMC Scholia
- The presence of IGHG1 in human pancreatic carcinomas is associated with immune evasion mechanisms. Li X, Ni R, Chen J, Liu Z, Xiao M, Jiang F, et al. Pancreas. 2011 Jul;40(5):753–61. PubMed Europe PMC Scholia
- Human NK cell lytic granules and regulation of their exocytosis. Krzewski K, Coligan JE. Front Immunol. 2012 Nov 9;3:335. PubMed Europe PMC Scholia
- Metalloprotease-mediated tumor cell shedding of B7-H6, the ligand of the natural killer cell-activating receptor NKp30. Schlecker E, Fiegler N, Arnold A, Altevogt P, Rose-John S, Moldenhauer G, et al. Cancer Res. 2014 Jul 1;74(13):3429–40. PubMed Europe PMC Scholia
- The proto-oncogene Myc drives expression of the NK cell-activating NKp30 ligand B7-H6 in tumor cells. Textor S, Bossler F, Henrich KO, Gartlgruber M, Pollmann J, Fiegler N, et al. Oncoimmunology. 2016 Jul 28;5(7):e1116674. PubMed Europe PMC Scholia
- Drug resistance in pancreatic cancer: Impact of altered energy metabolism. Grasso C, Jansen G, Giovannetti E. Crit Rev Oncol Hematol. 2017 Jun;114:139–52. PubMed Europe PMC Scholia
- Natural killer cells and their therapeutic role in pancreatic cancer: A systematic review. Van Audenaerde JRM, Roeyen G, Darcy PK, Kershaw MH, Peeters M, Smits ELJ. Pharmacol Ther. 2018 Sep;189:31–44. PubMed Europe PMC Scholia
- CD226 regulates natural killer cell antitumor responses via phosphorylation-mediated inactivation of transcription factor FOXO1. Du X, de Almeida P, Manieri N, de Almeida Nagata D, Wu TD, Harden Bowles K, et al. Proc Natl Acad Sci U S A. 2018 Dec 11;115(50):E11731–40. PubMed Europe PMC Scholia
- High glucose promotes pancreatic cancer cells to escape from immune surveillance via AMPK-Bmi1-GATA2-MICA/B pathway. Duan Q, Li H, Gao C, Zhao H, Wu S, Wu H, et al. J Exp Clin Cancer Res. 2019 May 14;38(1):192. PubMed Europe PMC Scholia
- The Natural Cytotoxicity Receptors in Health and Disease. Barrow AD, Martin CJ, Colonna M. Front Immunol. 2019 May 7;10:909. PubMed Europe PMC Scholia
- NKG2D and MICA/B shedding: a “tag game” between NK cells and malignant cells. Xing S, Ferrari de Andrade L. Clin Transl Immunology. 2020 Dec 22;9(12):e1230. PubMed Europe PMC Scholia