Caspase-2 and oxidative stress underlie the immunogenic potential of high hydrostatic pressure-induced cancer cell death

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10373907" target="_blank" >RIV/00216208:11130/17:10373907 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064203:_____/17:10373907

Výsledek na webu

<a href="https://doi.org/10.1080/2162402X.2016.1258505" target="_blank" >https://doi.org/10.1080/2162402X.2016.1258505</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/2162402X.2016.1258505" target="_blank" >10.1080/2162402X.2016.1258505</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Caspase-2 and oxidative stress underlie the immunogenic potential of high hydrostatic pressure-induced cancer cell death

Popis výsledku v původním jazyce

High hydrostatic pressure (HHP) promotes key characteristics of immunogenic cell death (ICD), in thus far resembling immunogenic chemotherapy and ionizing irradiation. Here, we demonstrate that cancer cells succumbing to HHP induce CD4(+) and CD8(+) T cell-dependent protective immunity in vivo. Moreover, we show that cell death induction by HHP relies on the overproduction of reactive oxygen species (ROS), causing rapid establishment of the integrated stress response, eIF2 alpha phosphorylation by PERK, and sequential caspase-2, -8 and -3 activation. Non-phosphorylatable eIF2 alpha, depletion of PERK, caspase-2 or -8 compromised calreticulin exposure by cancer cells succumbing to HHP but could not inhibit death. Interestingly, the phagocytosis of HHP-treated malignant cells by dendritic cells was suppressed by the knockdown of caspase-2 in the former. Thus, caspase-2 mediates a key function in the interaction between dying cancer cells and antigen presenting cells. Our results indicate that the ROS -&gt; PERK -&gt; eIF2 alpha -&gt; caspase-2 signaling pathway is central for the perception of HHP-driven cell death as immunogenic.

Název v anglickém jazyce

Caspase-2 and oxidative stress underlie the immunogenic potential of high hydrostatic pressure-induced cancer cell death

Popis výsledku anglicky

High hydrostatic pressure (HHP) promotes key characteristics of immunogenic cell death (ICD), in thus far resembling immunogenic chemotherapy and ionizing irradiation. Here, we demonstrate that cancer cells succumbing to HHP induce CD4(+) and CD8(+) T cell-dependent protective immunity in vivo. Moreover, we show that cell death induction by HHP relies on the overproduction of reactive oxygen species (ROS), causing rapid establishment of the integrated stress response, eIF2 alpha phosphorylation by PERK, and sequential caspase-2, -8 and -3 activation. Non-phosphorylatable eIF2 alpha, depletion of PERK, caspase-2 or -8 compromised calreticulin exposure by cancer cells succumbing to HHP but could not inhibit death. Interestingly, the phagocytosis of HHP-treated malignant cells by dendritic cells was suppressed by the knockdown of caspase-2 in the former. Thus, caspase-2 mediates a key function in the interaction between dying cancer cells and antigen presenting cells. Our results indicate that the ROS -&gt; PERK -&gt; eIF2 alpha -&gt; caspase-2 signaling pathway is central for the perception of HHP-driven cell death as immunogenic.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

OncoImmunology [online]

ISSN

2162-402X

e-ISSN

—

Svazek periodika

6

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

—

Kód UT WoS článku

000397069400003

EID výsledku v databázi Scopus

2-s2.0-85008177096