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 Willighagen

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Homo sapiens

Communities

PancCanNet

Annotations

Cell Type Ontology

malignant cell natural killer cell

Pathway Ontology

pancreatic cancer pathway

Disease Ontology

pancreatic cancer

Participants

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
MICB Protein uniprot:F5H7Q8
MICA Protein uniprot:A0A024RCL3
NCR3LG1 Protein uniprot:Q68D85 B7H6
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
KLRK1 Protein uniprot:P26718 NKG2-D
GZMB Protein uniprot:P10144 Granzyme B
PRF1 Protein uniprot:P14222 Perforin-1

References

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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