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Surface-exposed and soluble calreticulin: conflicting biomarkers for cancer prognosis

Increased exposure of calreticulin (CALR) on malignant cells is associated with therapy-relevant adaptive immune responses and superior therapeutic outcome in solid tumors and haemato-oncological diseases, because surface-exposed CALR acts as an ‘eat-me’ signal facilitating the phagocytosis of stres...

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Autores principales: Kepp, Oliver, Liu, Peng, Zhao, Liwei, Plo, Isabelle, Kroemer, Guido
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458660/
https://www.ncbi.nlm.nih.gov/pubmed/32923154
http://dx.doi.org/10.1080/2162402X.2020.1792037
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author Kepp, Oliver
Liu, Peng
Zhao, Liwei
Plo, Isabelle
Kroemer, Guido
author_facet Kepp, Oliver
Liu, Peng
Zhao, Liwei
Plo, Isabelle
Kroemer, Guido
author_sort Kepp, Oliver
collection PubMed
description Increased exposure of calreticulin (CALR) on malignant cells is associated with therapy-relevant adaptive immune responses and superior therapeutic outcome in solid tumors and haemato-oncological diseases, because surface-exposed CALR acts as an ‘eat-me’ signal facilitating the phagocytosis of stressed and dying cancer cells by immature dendritic cells, thus favoring antitumor immune responses. On the contrary, mutations of the CALR gene that cause the omission of the C-terminal KDEL endoplasmic reticulum retention motif from CALR protein, resulting in its secretion from cells, act as oncogenic drivers in myeloproliferative neoplasms via the autocrine activation of the thrombopoietin receptor. We recently showed that soluble CALR inhibited the phagocytosis of cancer cells by dendritic cells, thus dampening anticancer immune responses. Furthermore, systemic elevations of soluble CALR that is secreted from tumors or that is artificially supplied by injection of the recombinant protein decreased the efficacy of immunotherapy. Thus, depending on its location, CALR can have immunostimulatory or immunosuppressive functions.
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spelling pubmed-74586602020-09-11 Surface-exposed and soluble calreticulin: conflicting biomarkers for cancer prognosis Kepp, Oliver Liu, Peng Zhao, Liwei Plo, Isabelle Kroemer, Guido Oncoimmunology Brief Report Increased exposure of calreticulin (CALR) on malignant cells is associated with therapy-relevant adaptive immune responses and superior therapeutic outcome in solid tumors and haemato-oncological diseases, because surface-exposed CALR acts as an ‘eat-me’ signal facilitating the phagocytosis of stressed and dying cancer cells by immature dendritic cells, thus favoring antitumor immune responses. On the contrary, mutations of the CALR gene that cause the omission of the C-terminal KDEL endoplasmic reticulum retention motif from CALR protein, resulting in its secretion from cells, act as oncogenic drivers in myeloproliferative neoplasms via the autocrine activation of the thrombopoietin receptor. We recently showed that soluble CALR inhibited the phagocytosis of cancer cells by dendritic cells, thus dampening anticancer immune responses. Furthermore, systemic elevations of soluble CALR that is secreted from tumors or that is artificially supplied by injection of the recombinant protein decreased the efficacy of immunotherapy. Thus, depending on its location, CALR can have immunostimulatory or immunosuppressive functions. Taylor & Francis 2020-07-20 /pmc/articles/PMC7458660/ /pubmed/32923154 http://dx.doi.org/10.1080/2162402X.2020.1792037 Text en © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Brief Report
Kepp, Oliver
Liu, Peng
Zhao, Liwei
Plo, Isabelle
Kroemer, Guido
Surface-exposed and soluble calreticulin: conflicting biomarkers for cancer prognosis
title Surface-exposed and soluble calreticulin: conflicting biomarkers for cancer prognosis
title_full Surface-exposed and soluble calreticulin: conflicting biomarkers for cancer prognosis
title_fullStr Surface-exposed and soluble calreticulin: conflicting biomarkers for cancer prognosis
title_full_unstemmed Surface-exposed and soluble calreticulin: conflicting biomarkers for cancer prognosis
title_short Surface-exposed and soluble calreticulin: conflicting biomarkers for cancer prognosis
title_sort surface-exposed and soluble calreticulin: conflicting biomarkers for cancer prognosis
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458660/
https://www.ncbi.nlm.nih.gov/pubmed/32923154
http://dx.doi.org/10.1080/2162402X.2020.1792037
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