Interactions of natural killer cells in pancreatic cancer (Homo sapiens)

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Nucleus Natural killer cell Nucleus994, 95, 9979, 10148107151199, 1099158989999, 109, 114, 107 Tumor cellShedding of MICA/Bcomplex prevents binding of KLRK1 to tumor cellNatural killer cell adhesionIGHG1 andIgE bindcompetitivelyto FCGR3ANCR3LG1ApoptosisNCR3MICBGATA2MICABMI1NCR1ULBP1GATA239469310310MICBMICA10ADAM17ADAM1044NCR3LG1MYC4, 7NCR3LG1PVR74PVR9IGHG111IGHG1Glycolysis9, 112, 9glucoseIgE314lactate2, 9KLRK13KLRK1PRF19GZMB6, 136, 13CCL1CCL4CCL5CCL3GM-CSFTNFCCL2CXCL8Innate immune responseAdaptive immune responseNCR31, 4CD226FOXO14CD968IFNG4TIGIT4NCR1FCGR3A1KLRK14, 11, 123GZMBPRF16, 136, 13


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).

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  1. Barrow AD, Martin CJ, Colonna M; ''The Natural Cytotoxicity Receptors in Health and Disease.''; Front Immunol, 2019 PubMed Europe PMC Scholia
  2. Grasso C, Jansen G, Giovannetti E; ''Drug resistance in pancreatic cancer: Impact of altered energy metabolism.''; Crit Rev Oncol Hematol, 2017 PubMed Europe PMC Scholia
  3. Duan Q, Li H, Gao C, Zhao H, Wu S, Wu H, Wang C, Shen Q, Yin T; ''High glucose promotes pancreatic cancer cells to escape from immune surveillance via AMPK-Bmi1-GATA2-MICA/B pathway.''; J Exp Clin Cancer Res, 2019 PubMed Europe PMC Scholia
  4. Van Audenaerde JRM, Roeyen G, Darcy PK, Kershaw MH, Peeters M, Smits ELJ; ''Natural killer cells and their therapeutic role in pancreatic cancer: A systematic review.''; Pharmacol Ther, 2018 PubMed Europe PMC Scholia
  5. Textor S, Bossler F, Henrich KO, Gartlgruber M, Pollmann J, Fiegler N, Arnold A, Westermann F, Waldburger N, Breuhahn K, Golfier S, Witzens-Harig M, Cerwenka A; ''The proto-oncogene Myc drives expression of the NK cell-activating NKp30 ligand B7-H6 in tumor cells.''; Oncoimmunology, 2016 PubMed Europe PMC Scholia
  6. Pardo J, Balkow S, Anel A, Simon MM; ''Granzymes are essential for natural killer cell-mediated and perf-facilitated tumor control.''; Eur J Immunol, 2002 PubMed Europe PMC Scholia
  7. Schlecker E, Fiegler N, Arnold A, Altevogt P, Rose-John S, Moldenhauer G, Sucker A, Paschen A, von Strandmann EP, Textor S, Cerwenka A; ''Metalloprotease-mediated tumor cell shedding of B7-H6, the ligand of the natural killer cell-activating receptor NKp30.''; Cancer Res, 2014 PubMed Europe PMC Scholia
  8. Du X, de Almeida P, Manieri N, de Almeida Nagata D, Wu TD, Harden Bowles K, Arumugam V, Schartner J, Cubas R, Mittman S, Javinal V, Anderson KR, Warming S, Grogan JL, Chiang EY; ''CD226 regulates natural killer cell antitumor responses via phosphorylation-mediated inactivation of transcription factor FOXO1.''; Proc Natl Acad Sci U S A, 2018 PubMed Europe PMC Scholia
  9. Van Audenaerde JRM, Roeyen G, Darcy PK, Kershaw MH, Peeters M, Smits ELJ; ''Natural killer cells and their therapeutic role in pancreatic cancer: A systematic review.''; Pharmacol Ther, 2018 PubMed Europe PMC Scholia
  10. Xing S, Ferrari de Andrade L; ''NKG2D and MICA/B shedding: a 'tag game' between NK cells and malignant cells.''; Clin Transl Immunology, 2020 PubMed Europe PMC Scholia
  11. Li X, Ni R, Chen J, Liu Z, Xiao M, Jiang F, Lu C; ''The presence of IGHG1 in human pancreatic carcinomas is associated with immune evasion mechanisms.''; Pancreas, 2011 PubMed Europe PMC Scholia
  12. Cooper MA, Fehniger TA, Caligiuri MA; ''The biology of human natural killer-cell subsets.''; Trends Immunol, 2001 PubMed Europe PMC Scholia
  13. Voskoboinik I, Dunstone MA, Baran K, Whisstock JC, Trapani JA; ''Perforin: structure, function, and role in human immunopathology.''; Immunol Rev, 2010 PubMed Europe PMC Scholia
  14. Fu SL, Pierre J, Smith-Norowitz TA, Hagler M, Bowne W, Pincus MR, Mueller CM, Zenilman ME, Bluth MH; ''Immunoglobulin E antibodies from pancreatic cancer patients mediate antibody-dependent cell-mediated cytotoxicity against pancreatic cancer cells.''; Clin Exp Immunol, 2008 PubMed Europe PMC Scholia
  15. Krzewski K, Coligan JE; ''Human NK cell lytic granules and regulation of their exocytosis.''; Front Immunol, 2012 PubMed Europe PMC Scholia


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119997view07:19, 9 October 2021EgonwNot a conversion
119992view06:49, 8 October 2021EgonwNot a conversion
119203view12:02, 22 June 2021MkutmonReverted to version '16:10, 20 June 2021' by Mkutmon
119202view10:16, 22 June 2021Mkutmonupdate layout
119181view16:10, 20 June 2021NKnoopsAdded references
119077view14:33, 15 June 2021NKnoopscomplex creation MYC and NCR3LG1 genes
119076view13:54, 15 June 2021NKnoopsChange Protein annotation
118964view11:02, 5 June 2021EweitzFix two interactions
118963view10:59, 5 June 2021EweitzRefine capitalization
118324view10:04, 27 May 2021NKnoopsGene node changes according to HGNC and addition of references
117092view09:39, 17 May 2021MkutmonUpdate layout
116522view11:05, 7 May 2021NKnoopsMainly layout changes have been made. Furthermore, the genes for the NKp30 and NKp46 proteins have been added. Finally, an update to the pathway description has been made as well.
116352view11:41, 3 May 2021MkutmonOntology Term : 'malignant cell' added !
116351view11:41, 3 May 2021MkutmonOntology Term : 'natural killer cell' added !
116350view11:40, 3 May 2021MkutmonOntology Term : 'pancreatic cancer pathway' added !
116349view11:40, 3 May 2021MkutmonOntology Term : 'pancreatic cancer' added !
116344view17:34, 2 May 2021NKnoopsNew pathway

External references


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NameTypeDatabase referenceComment
ADAM10GeneProductENSG00000137845 (Ensembl)
ADAM17GeneProductENSG00000151694 (Ensembl)
ApoptosisPathwayWP254 (WikiPathways)
BMI1GeneProductENSG00000168283 (Ensembl)
CCL1GeneProductENSG00000108702 (Ensembl)
CCL2GeneProductENSG00000108691 (Ensembl)
CCL3GeneProductENSG00000277632 (Ensembl)
CCL4GeneProductENSG00000275302 (Ensembl)
CCL5GeneProductENSG00000271503 (Ensembl)
CD226ProteinQ15762 (Uniprot-TrEMBL) DNAM1
CD96ProteinP40200 (Uniprot-TrEMBL) TACTILE
CXCL8MetaboliteCHEBI:138181 (ChEBI)
FCGR3AProteinP08637 (Uniprot-TrEMBL) FcγRIII
FOXO1GeneProductENSG00000150907 (Ensembl)
GATA2GeneProductENSG00000179348 (Ensembl)
GATA2ProteinP23769 (Uniprot-TrEMBL)
GM-CSFProteinP04141 (Uniprot-TrEMBL)
GZMBProteinP10144 (Uniprot-TrEMBL) Granzyme B
GlycolysisPathwayWP534 (WikiPathways)
IFNGGeneProductENSG00000111537 (Ensembl) IFNγ
IGHG1GeneProductENSG00000211896 (Ensembl)
IGHG1ProteinP01857 (Uniprot-TrEMBL)
IgEProteinQ79455 (Wikidata)
KLRK1GeneProductENSG00000213809 (Ensembl)
KLRK1ProteinP26718 (Uniprot-TrEMBL) NKG2-D
MICAProteinA0A024RCL3 (Uniprot-TrEMBL)
MICBProteinF5H7Q8 (Uniprot-TrEMBL)
MYCGeneProductENSG00000136997 (Ensembl)
NCR1GeneProductENSG00000189430 (Ensembl)
NCR1ProteinO76036 (Uniprot-TrEMBL) NKp46
NCR3GeneProductENSG00000204475 (Ensembl)
NCR3LG1GeneProductENSG00000188211 (Ensembl)
NCR3LG1ProteinQ68D85 (Uniprot-TrEMBL) B7H6
NCR3ProteinO14931 (Uniprot-TrEMBL) NKp30
PRF1ProteinP14222 (Uniprot-TrEMBL) Perforin-1
PVRGeneProductENSG00000073008 (Ensembl)
PVRProteinP15151 (Uniprot-TrEMBL) CD155
TIGITProteinQ495A1 (Uniprot-TrEMBL)
TNFGeneProductENSG00000232810 (Ensembl) TNFα
ULBP1ProteinP16757 (Uniprot-TrEMBL) UL16
glucoseMetaboliteCHEBI:17234 (ChEBI)
lactateMetaboliteCHEBI:24996 (ChEBI)

Annotated Interactions

No annotated interactions

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