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Mechanisms of Apoptosis Resistance to NK Cell-Mediated Cytotoxicity in Cancer

1
Department of Functional Biology, Immunology, University of Oviedo, 33006 Oviedo, Spain
2
Instituto Universitario de Oncología del Principado de Asturias, IUOPA, 33006 Oviedo, Spain
3
Instituto de Investigación Biosanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
4
Department of Hematology, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Spain
5
Department of Biochemistry and Molecular Biology, University of Oviedo, 33006 Oviedo, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Int. J. Mol. Sci. 2020, 21(10), 3726; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103726
Received: 21 April 2020 / Revised: 20 May 2020 / Accepted: 22 May 2020 / Published: 25 May 2020
(This article belongs to the Special Issue Survival Pathways Involved in Resistance to Apoptosis in Cancer)
Natural killer (NK) cells are major contributors to immunosurveillance and control of tumor development by inducing apoptosis of malignant cells. Among the main mechanisms involved in NK cell-mediated cytotoxicity, the death receptor pathway and the release of granules containing perforin/granzymes stand out due to their efficacy in eliminating tumor cells. However, accumulated evidence suggest a profound immune suppression in the context of tumor progression affecting effector cells, such as NK cells, leading to decreased cytotoxicity. This diminished capability, together with the development of resistance to apoptosis by cancer cells, favor the loss of immunogenicity and promote immunosuppression, thus partially inducing NK cell-mediated killing resistance. Altered expression patterns of pro- and anti-apoptotic proteins along with genetic background comprise the main mechanisms of resistance to NK cell-related apoptosis. Herein, we summarize the main effector cytotoxic mechanisms against tumor cells, as well as the major resistance strategies acquired by tumor cells that hamper the extrinsic and intrinsic apoptotic pathways related to NK cell-mediated killing. View Full-Text
Keywords: NK cell; apoptosis; granzymes; perforin; death receptors; Trail; FasL; Fas; granulysin; apoptosis resistance NK cell; apoptosis; granzymes; perforin; death receptors; Trail; FasL; Fas; granulysin; apoptosis resistance
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MDPI and ACS Style

Sordo-Bahamonde, C.; Lorenzo-Herrero, S.; Payer, Á.R.; Gonzalez, S.; López-Soto, A. Mechanisms of Apoptosis Resistance to NK Cell-Mediated Cytotoxicity in Cancer. Int. J. Mol. Sci. 2020, 21, 3726. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103726

AMA Style

Sordo-Bahamonde C, Lorenzo-Herrero S, Payer ÁR, Gonzalez S, López-Soto A. Mechanisms of Apoptosis Resistance to NK Cell-Mediated Cytotoxicity in Cancer. International Journal of Molecular Sciences. 2020; 21(10):3726. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103726

Chicago/Turabian Style

Sordo-Bahamonde, Christian, Seila Lorenzo-Herrero, Ángel R. Payer, Segundo Gonzalez, and Alejandro López-Soto. 2020. "Mechanisms of Apoptosis Resistance to NK Cell-Mediated Cytotoxicity in Cancer" International Journal of Molecular Sciences 21, no. 10: 3726. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103726

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