Cargando…

All About (NK Cell-Mediated) Death in Two Acts and an Unexpected Encore: Initiation, Execution and Activation of Adaptive Immunity

NK cells are key mediators of immune cell-mediated cytotoxicity toward infected and transformed cells, being one of the main executors of cell death in the immune system. NK cells recognize target cells through an array of inhibitory and activating receptors for endogenous or exogenous pathogen-deri...

Descripción completa

Detalles Bibliográficos
Autores principales: Ramírez-Labrada, Ariel, Pesini, Cecilia, Santiago, Llipsy, Hidalgo, Sandra, Calvo-Pérez, Adanays, Oñate, Carmen, Andrés-Tovar, Alejandro, Garzón-Tituaña, Marcela, Uranga-Murillo, Iratxe, Arias, Maykel A., Galvez, Eva M., Pardo, Julián
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149431/
https://www.ncbi.nlm.nih.gov/pubmed/35651603
http://dx.doi.org/10.3389/fimmu.2022.896228
_version_ 1784717208704778240
author Ramírez-Labrada, Ariel
Pesini, Cecilia
Santiago, Llipsy
Hidalgo, Sandra
Calvo-Pérez, Adanays
Oñate, Carmen
Andrés-Tovar, Alejandro
Garzón-Tituaña, Marcela
Uranga-Murillo, Iratxe
Arias, Maykel A.
Galvez, Eva M.
Pardo, Julián
author_facet Ramírez-Labrada, Ariel
Pesini, Cecilia
Santiago, Llipsy
Hidalgo, Sandra
Calvo-Pérez, Adanays
Oñate, Carmen
Andrés-Tovar, Alejandro
Garzón-Tituaña, Marcela
Uranga-Murillo, Iratxe
Arias, Maykel A.
Galvez, Eva M.
Pardo, Julián
author_sort Ramírez-Labrada, Ariel
collection PubMed
description NK cells are key mediators of immune cell-mediated cytotoxicity toward infected and transformed cells, being one of the main executors of cell death in the immune system. NK cells recognize target cells through an array of inhibitory and activating receptors for endogenous or exogenous pathogen-derived ligands, which together with adhesion molecules form a structure known as immunological synapse that regulates NK cell effector functions. The main and best characterized mechanisms involved in NK cell-mediated cytotoxicity are the granule exocytosis pathway (perforin/granzymes) and the expression of death ligands. These pathways are recognized as activators of different cell death programmes on the target cells leading to their destruction. However, most studies analyzing these pathways have used pure recombinant or native proteins instead of intact NK cells and, thus, extrapolation of the results to NK cell-mediated cell death might be difficult. Specially, since the activation of granule exocytosis and/or death ligands during NK cell-mediated elimination of target cells might be influenced by the stimulus received from target cells and other microenvironment components, which might affect the cell death pathways activated on target cells. Here we will review and discuss the available experimental evidence on how NK cells kill target cells, with a special focus on the different cell death modalities that have been found to be activated during NK cell-mediated cytotoxicity; including apoptosis and more inflammatory pathways like necroptosis and pyroptosis. In light of this new evidence, we will develop the new concept of cell death induced by NK cells as a new regulatory mechanism linking innate immune response with the activation of tumour adaptive T cell responses, which might be the initiating stimulus that trigger the cancer-immunity cycle. The use of the different cell death pathways and the modulation of the tumour cell molecular machinery regulating them might affect not only tumour cell elimination by NK cells but, in addition, the generation of T cell responses against the tumour that would contribute to efficient tumour elimination and generate cancer immune memory preventing potential recurrences.
format Online
Article
Text
id pubmed-9149431
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-91494312022-05-31 All About (NK Cell-Mediated) Death in Two Acts and an Unexpected Encore: Initiation, Execution and Activation of Adaptive Immunity Ramírez-Labrada, Ariel Pesini, Cecilia Santiago, Llipsy Hidalgo, Sandra Calvo-Pérez, Adanays Oñate, Carmen Andrés-Tovar, Alejandro Garzón-Tituaña, Marcela Uranga-Murillo, Iratxe Arias, Maykel A. Galvez, Eva M. Pardo, Julián Front Immunol Immunology NK cells are key mediators of immune cell-mediated cytotoxicity toward infected and transformed cells, being one of the main executors of cell death in the immune system. NK cells recognize target cells through an array of inhibitory and activating receptors for endogenous or exogenous pathogen-derived ligands, which together with adhesion molecules form a structure known as immunological synapse that regulates NK cell effector functions. The main and best characterized mechanisms involved in NK cell-mediated cytotoxicity are the granule exocytosis pathway (perforin/granzymes) and the expression of death ligands. These pathways are recognized as activators of different cell death programmes on the target cells leading to their destruction. However, most studies analyzing these pathways have used pure recombinant or native proteins instead of intact NK cells and, thus, extrapolation of the results to NK cell-mediated cell death might be difficult. Specially, since the activation of granule exocytosis and/or death ligands during NK cell-mediated elimination of target cells might be influenced by the stimulus received from target cells and other microenvironment components, which might affect the cell death pathways activated on target cells. Here we will review and discuss the available experimental evidence on how NK cells kill target cells, with a special focus on the different cell death modalities that have been found to be activated during NK cell-mediated cytotoxicity; including apoptosis and more inflammatory pathways like necroptosis and pyroptosis. In light of this new evidence, we will develop the new concept of cell death induced by NK cells as a new regulatory mechanism linking innate immune response with the activation of tumour adaptive T cell responses, which might be the initiating stimulus that trigger the cancer-immunity cycle. The use of the different cell death pathways and the modulation of the tumour cell molecular machinery regulating them might affect not only tumour cell elimination by NK cells but, in addition, the generation of T cell responses against the tumour that would contribute to efficient tumour elimination and generate cancer immune memory preventing potential recurrences. Frontiers Media S.A. 2022-05-16 /pmc/articles/PMC9149431/ /pubmed/35651603 http://dx.doi.org/10.3389/fimmu.2022.896228 Text en Copyright © 2022 Ramírez-Labrada, Pesini, Santiago, Hidalgo, Calvo-Pérez, Oñate, Andrés-Tovar, Garzón-Tituaña, Uranga-Murillo, Arias, Galvez and Pardo https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ramírez-Labrada, Ariel
Pesini, Cecilia
Santiago, Llipsy
Hidalgo, Sandra
Calvo-Pérez, Adanays
Oñate, Carmen
Andrés-Tovar, Alejandro
Garzón-Tituaña, Marcela
Uranga-Murillo, Iratxe
Arias, Maykel A.
Galvez, Eva M.
Pardo, Julián
All About (NK Cell-Mediated) Death in Two Acts and an Unexpected Encore: Initiation, Execution and Activation of Adaptive Immunity
title All About (NK Cell-Mediated) Death in Two Acts and an Unexpected Encore: Initiation, Execution and Activation of Adaptive Immunity
title_full All About (NK Cell-Mediated) Death in Two Acts and an Unexpected Encore: Initiation, Execution and Activation of Adaptive Immunity
title_fullStr All About (NK Cell-Mediated) Death in Two Acts and an Unexpected Encore: Initiation, Execution and Activation of Adaptive Immunity
title_full_unstemmed All About (NK Cell-Mediated) Death in Two Acts and an Unexpected Encore: Initiation, Execution and Activation of Adaptive Immunity
title_short All About (NK Cell-Mediated) Death in Two Acts and an Unexpected Encore: Initiation, Execution and Activation of Adaptive Immunity
title_sort all about (nk cell-mediated) death in two acts and an unexpected encore: initiation, execution and activation of adaptive immunity
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149431/
https://www.ncbi.nlm.nih.gov/pubmed/35651603
http://dx.doi.org/10.3389/fimmu.2022.896228
work_keys_str_mv AT ramirezlabradaariel allaboutnkcellmediateddeathintwoactsandanunexpectedencoreinitiationexecutionandactivationofadaptiveimmunity
AT pesinicecilia allaboutnkcellmediateddeathintwoactsandanunexpectedencoreinitiationexecutionandactivationofadaptiveimmunity
AT santiagollipsy allaboutnkcellmediateddeathintwoactsandanunexpectedencoreinitiationexecutionandactivationofadaptiveimmunity
AT hidalgosandra allaboutnkcellmediateddeathintwoactsandanunexpectedencoreinitiationexecutionandactivationofadaptiveimmunity
AT calvoperezadanays allaboutnkcellmediateddeathintwoactsandanunexpectedencoreinitiationexecutionandactivationofadaptiveimmunity
AT onatecarmen allaboutnkcellmediateddeathintwoactsandanunexpectedencoreinitiationexecutionandactivationofadaptiveimmunity
AT andrestovaralejandro allaboutnkcellmediateddeathintwoactsandanunexpectedencoreinitiationexecutionandactivationofadaptiveimmunity
AT garzontituanamarcela allaboutnkcellmediateddeathintwoactsandanunexpectedencoreinitiationexecutionandactivationofadaptiveimmunity
AT urangamurilloiratxe allaboutnkcellmediateddeathintwoactsandanunexpectedencoreinitiationexecutionandactivationofadaptiveimmunity
AT ariasmaykela allaboutnkcellmediateddeathintwoactsandanunexpectedencoreinitiationexecutionandactivationofadaptiveimmunity
AT galvezevam allaboutnkcellmediateddeathintwoactsandanunexpectedencoreinitiationexecutionandactivationofadaptiveimmunity
AT pardojulian allaboutnkcellmediateddeathintwoactsandanunexpectedencoreinitiationexecutionandactivationofadaptiveimmunity