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Trends Cancer. 2017 Jun;3(6):407-422. doi: 10.1016/j.trecan.2017.04.001. Epub 2017 Jun 9.

The Untold Story of Granzymes in Oncoimmunology: Novel Opportunities with Old Acquaintances.

Author information

1
Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragon (CIBA), 50009 Zaragoza, Spain; These authors contributed equally to this work.
2
Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragon (CIBA), 50009 Zaragoza, Spain; Department of Biochemistry and Molecular and Cell Biology, and Department of Microbiology, Preventive Medicine, and Public Health, University of Zaragoza, 50009 Zaragoza, Spain; Servicio de Inmunología Hospital Clínico Universitario Lorenzo Blesa, Zaragoza, Spain; Nanoscience Institute of Aragon (INA), University of Zaragoza, 50018 Zaragoza, Spain; These authors contributed equally to this work.
3
Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragon (CIBA), 50009 Zaragoza, Spain.
4
Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragon (CIBA), 50009 Zaragoza, Spain; Servicio de Aparato Digestivo, Hospital Clínico Universitario Lorenzo Blesa, Zaragoza, Spain.
5
International Collaboration on Repair Discoveries (ICORD), Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
6
Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Biomedical Research Centre of Aragon (CIBA), 50009 Zaragoza, Spain; Department of Biochemistry and Molecular and Cell Biology, and Department of Microbiology, Preventive Medicine, and Public Health, University of Zaragoza, 50009 Zaragoza, Spain; Nanoscience Institute of Aragon (INA), University of Zaragoza, 50018 Zaragoza, Spain; Aragon I+D Foundation (ARAID), Zaragoza, Spain. Electronic address: pardojim@unizar.es.

Abstract

For more than 20 years perforin and granzymes (GZMs) have been recognized as key cell death executors of cytotoxic T (Tc) and natural killer (NK) cells during cancer immunosurveillance. In immune surveillance, perforin and GZMB, the most potent cytotoxic molecules, act mainly as antitumoral and anti-infectious factors. However, when expressed by immune regulatory cells they may contribute to immune evasion of specific cancer types. By contrast, the other major granzyme, GZMA, seems not to play a major role in Tc/NK cell-mediated cytotoxicity, but acts as a proinflammatory cytokine that might contribute to cancer development. Members of the GZM family also regulate other biological processes unrelated to cell death, such as angiogenesis, vascular integrity, extracellular matrix remodeling, and barrier function, all of which contribute to cancer initiation and progression. Thus, a new paradigm is emerging in the field of oncoimmunology. Can GZMs act as protumoral factors under some circumstances? We review the diverse roles of GZMs in cancer progression, and new therapeutic opportunities emerging from targeting these protumoral roles.

KEYWORDS:

cancer progression; extracellular matrix; granzymes; inflammation

PMID:
28718416
DOI:
10.1016/j.trecan.2017.04.001
[Indexed for MEDLINE]

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