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Calreticulin exposure correlates with robust adaptive antitumor immunity and favorable prognosis in ovarian carcinoma patients
L. Kasikova, M. Hensler, I. Truxova, P. Skapa, J. Laco, L. Belicova, I. Praznovec, S. Vosahlikova, MJ. Halaska, T. Brtnicky, L. Rob, J. Presl, J. Kostun, I. Cremer, A. Ryska, G. Kroemer, L. Galluzzi, R. Spisek, J. Fucikova,
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem, Research Support, U.S. Gov't, Non-P.H.S.
NLK
BioMedCentral
od 2013-12-01 do 2019-12-31
BioMedCentral Open Access
od 2013
Directory of Open Access Journals
od 2013
Free Medical Journals
od 2013
PubMed Central
od 2013
Europe PubMed Central
od 2013
ProQuest Central
od 2013-05-01
Open Access Digital Library
od 2013-01-01
Open Access Digital Library
od 2013-01-01
Health & Medicine (ProQuest)
od 2013-05-01
ROAD: Directory of Open Access Scholarly Resources
od 2013
Springer Nature OA/Free Journals
od 2013-12-01 do 2019-12-31
- MeSH
- dospělí MeSH
- kalretikulin imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové mikroprostředí genetika imunologie MeSH
- nádory vaječníků genetika imunologie MeSH
- prognóza MeSH
- sekvenování transkriptomu MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stres endoplazmatického retikula MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
BACKGROUND: Adjuvanticity, which is the ability of neoplastic cells to deliver danger signals, is critical for the host immune system to mount spontaneous and therapy-driven anticancer immune responses. One of such signals, i.e., the exposure of calreticulin (CALR) on the membrane of malignant cells experiencing endoplasmic reticulum (ER) stress, is well known for its role in the activation of immune responses to dying cancer cells. However, the potential impact of CALR on the immune contexture of primary and metastatic high-grade serous carcinomas (HGSCs) and its prognostic value for patients with HGSC remains unclear. METHOD: We harnessed a retrospective cohort of primary (no = 152) and metastatic (no = 74) tumor samples from HGSC patients to investigate the CALR expression in relation with prognosis and function orientation of the tumor microenvironment. IHC data were complemented with transcriptomic and functional studies on second prospective cohort of freshly resected HGSC samples. In silico analysis of publicly available RNA expression data from 302 HGSC samples was used as a confirmatory approach. RESULTS: We demonstrate that CALR exposure on the surface of primary and metastatic HGSC cells is driven by a chemotherapy-independent ER stress response and culminates with the establishment of a local immune contexture characterized by TH1 polarization and cytotoxic activity that enables superior clinical benefits. CONCLUSIONS: Our data indicate that CALR levels in primary and metastatic HGSC samples have robust prognostic value linked to the activation of clinically-relevant innate and adaptive anticancer immune responses.
Citace poskytuje Crossref.org
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- $a Kasikova, Lenka $u Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, V Uvalu 84, 150 00, Prague 5, Czech Republic. Sotio, Prague, Czech Republic.
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- $a BACKGROUND: Adjuvanticity, which is the ability of neoplastic cells to deliver danger signals, is critical for the host immune system to mount spontaneous and therapy-driven anticancer immune responses. One of such signals, i.e., the exposure of calreticulin (CALR) on the membrane of malignant cells experiencing endoplasmic reticulum (ER) stress, is well known for its role in the activation of immune responses to dying cancer cells. However, the potential impact of CALR on the immune contexture of primary and metastatic high-grade serous carcinomas (HGSCs) and its prognostic value for patients with HGSC remains unclear. METHOD: We harnessed a retrospective cohort of primary (no = 152) and metastatic (no = 74) tumor samples from HGSC patients to investigate the CALR expression in relation with prognosis and function orientation of the tumor microenvironment. IHC data were complemented with transcriptomic and functional studies on second prospective cohort of freshly resected HGSC samples. In silico analysis of publicly available RNA expression data from 302 HGSC samples was used as a confirmatory approach. RESULTS: We demonstrate that CALR exposure on the surface of primary and metastatic HGSC cells is driven by a chemotherapy-independent ER stress response and culminates with the establishment of a local immune contexture characterized by TH1 polarization and cytotoxic activity that enables superior clinical benefits. CONCLUSIONS: Our data indicate that CALR levels in primary and metastatic HGSC samples have robust prognostic value linked to the activation of clinically-relevant innate and adaptive anticancer immune responses.
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