Dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response.

Over the last decade, several studies have extensively reported that activated natural killer (NK) cells can kill autologous immature dendritic cells (DCs) in vitro, whereas they spare fully activated DCs. This led to the proposal that activated NK cells might select a more immunogenic subset of DCs...

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Autores principales:	Barbara Morandi, Lorenzo Mortara, Laura Chiossone, Roberto S Accolla, Maria Cristina Mingari, Lorenzo Moretta, Alessandro Moretta, Guido Ferlazzo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/46d15d286ce54c5eac5555c69b6fd808
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spelling	oai:doaj.org-article:46d15d286ce54c5eac5555c69b6fd8082021-11-18T07:14:59ZDendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response.1932-620310.1371/journal.pone.0039170https://doaj.org/article/46d15d286ce54c5eac5555c69b6fd8082012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22723958/?tool=EBIhttps://doaj.org/toc/1932-6203Over the last decade, several studies have extensively reported that activated natural killer (NK) cells can kill autologous immature dendritic cells (DCs) in vitro, whereas they spare fully activated DCs. This led to the proposal that activated NK cells might select a more immunogenic subset of DCs during a protective immune response. However, there is no demonstration that autologous DC killing by NK cells is an event occurring in vivo and, consequently, the functional relevance of this killing remains elusive. Here we report that a significant decrease of CD11c(+) DCs was observed in draining lymph nodes of mice inoculated with MHC-devoid cells as NK cell targets able to induce NK cell activation. This in vivo DC editing by NK cells was perforin-dependent and it was functionally relevant, since residual lymph node DCs displayed an improved capability to induce T cell proliferation. In addition, in a model of anti-cancer vaccination, the administration of MHC-devoid cells together with tumor cells increased the number of tumor-specific CTLs and resulted in a significant increase in survival of mice upon challenge with a lethal dose of tumor cells. Depletion of NK cells or the use of perforin knockout mice strongly decreased the tumor-specific CTL expansion and its protective role against tumor cell challenge. As a whole, our data support the hypothesis that NK cell-mediated DC killing takes place in vivo and is able to promote expansion of cancer-specific CTLs. Our results also indicate that cancer vaccines could be improved by strategies aimed at activating NK cells.Barbara MorandiLorenzo MortaraLaura ChiossoneRoberto S AccollaMaria Cristina MingariLorenzo MorettaAlessandro MorettaGuido FerlazzoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39170 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Barbara Morandi Lorenzo Mortara Laura Chiossone Roberto S Accolla Maria Cristina Mingari Lorenzo Moretta Alessandro Moretta Guido Ferlazzo Dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response.
description	Over the last decade, several studies have extensively reported that activated natural killer (NK) cells can kill autologous immature dendritic cells (DCs) in vitro, whereas they spare fully activated DCs. This led to the proposal that activated NK cells might select a more immunogenic subset of DCs during a protective immune response. However, there is no demonstration that autologous DC killing by NK cells is an event occurring in vivo and, consequently, the functional relevance of this killing remains elusive. Here we report that a significant decrease of CD11c(+) DCs was observed in draining lymph nodes of mice inoculated with MHC-devoid cells as NK cell targets able to induce NK cell activation. This in vivo DC editing by NK cells was perforin-dependent and it was functionally relevant, since residual lymph node DCs displayed an improved capability to induce T cell proliferation. In addition, in a model of anti-cancer vaccination, the administration of MHC-devoid cells together with tumor cells increased the number of tumor-specific CTLs and resulted in a significant increase in survival of mice upon challenge with a lethal dose of tumor cells. Depletion of NK cells or the use of perforin knockout mice strongly decreased the tumor-specific CTL expansion and its protective role against tumor cell challenge. As a whole, our data support the hypothesis that NK cell-mediated DC killing takes place in vivo and is able to promote expansion of cancer-specific CTLs. Our results also indicate that cancer vaccines could be improved by strategies aimed at activating NK cells.
format	article
author	Barbara Morandi Lorenzo Mortara Laura Chiossone Roberto S Accolla Maria Cristina Mingari Lorenzo Moretta Alessandro Moretta Guido Ferlazzo
author_facet	Barbara Morandi Lorenzo Mortara Laura Chiossone Roberto S Accolla Maria Cristina Mingari Lorenzo Moretta Alessandro Moretta Guido Ferlazzo
author_sort	Barbara Morandi
title	Dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response.
title_short	Dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response.
title_full	Dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response.
title_fullStr	Dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response.
title_full_unstemmed	Dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response.
title_sort	dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/46d15d286ce54c5eac5555c69b6fd808
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Dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response.

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