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Cystatin C is gluco...
Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy.
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Kleeman, Sam O (author)
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Thakir, Tuba Mansoor (author)
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Demestichas, Breanna (author)
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Mourikis, Nicholas (author)
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Loiero, Dominik (author)
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Ferrer, Miriam (author)
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Bankier, Sean (author)
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Riazat-Kesh, Yosef J R A (author)
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Lee, Hassal (author)
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Chantzichristos, Dimitrios (author)
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Regan, Claire (author)
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Preall, Jonathan (author)
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Sinha, Sarthak (author)
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Rosin, Nicole (author)
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Yipp, Bryan (author)
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de Almeida, Luiz G N (author)
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Biernaskie, Jeff (author)
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Dufour, Antoine (author)
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Tober-Lau, Pinkus (author)
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Ruusalepp, Arno (author)
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- Bjorkegren, Johan L M (author)
- Karolinska Institutet
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Ralser, Markus (author)
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Kurth, Florian (author)
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Demichev, Vadim (author)
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Heywood, Todd (author)
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Gao, Qing (author)
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- Johannsson, Gudmundur, 1960 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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Koelzer, Viktor H (author)
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Walker, Brian R (author)
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Meyer, Hannah V (author)
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Janowitz, Tobias (author)
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Cell genomics. - 2666-979X. ; 3:8
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Cystatin C (CyC), a secreted cysteine protease inhibitor, has unclear biological functions. Many patients exhibit elevated plasma CyC levels, particularly during glucocorticoid (GC) treatment. This study links GCs with CyC's systemic regulation by utilizing genome-wide association and structural equation modeling to determine CyC production genetics in the UK Biobank. Both CyC production and a polygenic score (PGS) capturing predisposition to CyC production were associated with increased all-cause and cancer-specific mortality. We found that the GC receptor directly targets CyC, leading to GC-responsive CyC secretion in macrophages and cancer cells. CyC-knockout tumors displayed significantly reduced growth and diminished recruitment of TREM2+ macrophages, which have been connected to cancer immunotherapy failure. Furthermore, the CyC-production PGS predicted checkpoint immunotherapy failure in 685 patients with metastatic cancer from combined clinical trial cohorts. In conclusion, CyC may act as a GC effector pathway via TREM2+ macrophage recruitment and may be a potential target for combination cancer immunotherapy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Kleeman, Sam O
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Thakir, Tuba Man ...
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Demestichas, Bre ...
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Mourikis, Nichol ...
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Loiero, Dominik
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Ferrer, Miriam
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show more...
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Bankier, Sean
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Riazat-Kesh, Yos ...
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Lee, Hassal
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Chantzichristos, ...
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Regan, Claire
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Preall, Jonathan
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Sinha, Sarthak
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Rosin, Nicole
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Yipp, Bryan
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de Almeida, Luiz ...
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Biernaskie, Jeff
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Dufour, Antoine
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Tober-Lau, Pinku ...
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Ruusalepp, Arno
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Bjorkegren, Joha ...
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Ralser, Markus
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Kurth, Florian
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Demichev, Vadim
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Heywood, Todd
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Gao, Qing
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Johannsson, Gudm ...
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Koelzer, Viktor ...
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Walker, Brian R
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Meyer, Hannah V
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Janowitz, Tobias
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Cell genomics
- By the university
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University of Gothenburg
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Karolinska Institutet