Secreted calreticulin mutants subvert anticancer immunosurveillance
Mutations of the gene coding for calreticulin (CALR) that cause the loss of the C-terminal KDEL motif abolish its retention in the endoplasmic reticulum and cause CALR to be secreted from cells. Specific CALR mutants bearing a novel C-terminus can precipitate the manifestation of myeloproliferative...
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Online Access: | http://dx.doi.org/10.1080/2162402X.2019.1708126 |
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doaj-07193cac60174f6198f70e82ac1225ed2021-09-24T14:41:23ZengTaylor & Francis GroupOncoImmunology2162-402X2020-01-019110.1080/2162402X.2019.17081261708126Secreted calreticulin mutants subvert anticancer immunosurveillancePeng Liu0Liwei Zhao1Guido Kroemer2Oliver Kepp3Centre de Recherche des CordeliersCentre de Recherche des CordeliersCentre de Recherche des CordeliersCentre de Recherche des CordeliersMutations of the gene coding for calreticulin (CALR) that cause the loss of the C-terminal KDEL motif abolish its retention in the endoplasmic reticulum and cause CALR to be secreted from cells. Specific CALR mutants bearing a novel C-terminus can precipitate the manifestation of myeloproliferative diseases via the autocrine activation of the thrombopoietin receptor. We recently employed the retention using selective hooks (RUSH) technology to monitor CALR trafficking and demonstrated the secretion of C-terminally truncated variants of CALR in vitro and in vivo. Of note, extracellular CALR inhibited the phagocytosis of dying cancer cells by dendritic cells (DC). Via this mechanism, mutant CALR induced immunosuppression, which decreased the efficacy of immunogenic anticancer chemotherapies and PD-1 blockade.http://dx.doi.org/10.1080/2162402X.2019.1708126immunogenic cell deathretention using selective hookspd-1 blockade |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Peng Liu Liwei Zhao Guido Kroemer Oliver Kepp |
spellingShingle |
Peng Liu Liwei Zhao Guido Kroemer Oliver Kepp Secreted calreticulin mutants subvert anticancer immunosurveillance OncoImmunology immunogenic cell death retention using selective hooks pd-1 blockade |
author_facet |
Peng Liu Liwei Zhao Guido Kroemer Oliver Kepp |
author_sort |
Peng Liu |
title |
Secreted calreticulin mutants subvert anticancer immunosurveillance |
title_short |
Secreted calreticulin mutants subvert anticancer immunosurveillance |
title_full |
Secreted calreticulin mutants subvert anticancer immunosurveillance |
title_fullStr |
Secreted calreticulin mutants subvert anticancer immunosurveillance |
title_full_unstemmed |
Secreted calreticulin mutants subvert anticancer immunosurveillance |
title_sort |
secreted calreticulin mutants subvert anticancer immunosurveillance |
publisher |
Taylor & Francis Group |
series |
OncoImmunology |
issn |
2162-402X |
publishDate |
2020-01-01 |
description |
Mutations of the gene coding for calreticulin (CALR) that cause the loss of the C-terminal KDEL motif abolish its retention in the endoplasmic reticulum and cause CALR to be secreted from cells. Specific CALR mutants bearing a novel C-terminus can precipitate the manifestation of myeloproliferative diseases via the autocrine activation of the thrombopoietin receptor. We recently employed the retention using selective hooks (RUSH) technology to monitor CALR trafficking and demonstrated the secretion of C-terminally truncated variants of CALR in vitro and in vivo. Of note, extracellular CALR inhibited the phagocytosis of dying cancer cells by dendritic cells (DC). Via this mechanism, mutant CALR induced immunosuppression, which decreased the efficacy of immunogenic anticancer chemotherapies and PD-1 blockade. |
topic |
immunogenic cell death retention using selective hooks pd-1 blockade |
url |
http://dx.doi.org/10.1080/2162402X.2019.1708126 |
work_keys_str_mv |
AT pengliu secretedcalreticulinmutantssubvertanticancerimmunosurveillance AT liweizhao secretedcalreticulinmutantssubvertanticancerimmunosurveillance AT guidokroemer secretedcalreticulinmutantssubvertanticancerimmunosurveillance AT oliverkepp secretedcalreticulinmutantssubvertanticancerimmunosurveillance |
_version_ |
1717369717017018368 |