دورية أكاديمية
Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy
| العنوان: | Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy |
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| المؤلفون: | Kleeman, Sam O, Thakir, Tuba Mansoor, Demestichas, Breanna, Mourikis, Nicholas, Loiero, Dominik, Ferrer, Miriam, Bankier, Sean, Riazat-Kesh, Yosef J R A, Lee, Hassal, Chantzichristos, Dimitrios, Regan, Claire, Preall, Jonathan, Sinha, Sarthak, Rosin, Nicole, Yipp, Bryan, de Almeida, Luiz G N, Biernaskie, Jeff, Dufour, Antoine, Tober-Lau, Pinkus, Ruusalepp, Arno, Bjorkegren, Johan L M, Ralser, Markus, Kurth, Florian, Demichev, Vadim, Heywood, Todd, Gao, Qing, Johannsson, Gudmundur, Koelzer, Viktor H, Walker, Brian R, Meyer, Hannah V |
| المصدر: | Kleeman, Sam O; Thakir, Tuba Mansoor; Demestichas, Breanna; Mourikis, Nicholas; Loiero, Dominik; Ferrer, Miriam; Bankier, Sean; Riazat-Kesh, Yosef J R A; Lee, Hassal; Chantzichristos, Dimitrios; Regan, Claire; Preall, Jonathan; Sinha, Sarthak; Rosin, Nicole; Yipp, Bryan; de Almeida, Luiz G N; Biernaskie, Jeff; Dufour, Antoine; Tober-Lau, Pinkus; Ruusalepp, Arno; Bjorkegren, Johan L M; Ralser, Markus; Kurth, Florian; Demichev, Vadim; Heywood, Todd; Gao, Qing; Johannsson, Gudmundur; Koelzer, Viktor H; Walker, Brian R; Meyer, Hannah V; et al (2023). Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy. Cell Genomics, 3(8):100347. |
| بيانات النشر: | Cell Press (Elsevier) |
| سنة النشر: | 2023 |
| المجموعة: | University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| مصطلحات موضوعية: | Institute of Pathology and Molecular Pathology, 610 Medicine & health |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2666-979X |
| العلاقة: | https://www.zora.uzh.ch/id/eprint/251684/1/Kleemann_CellGen_2023.pdfTest; info:pmid/37601967; urn:issn:2666-979X |
| DOI: | 10.5167/uzh-251684 |
| DOI: | 10.1016/j.xgen.2023.100347 |
| الإتاحة: | https://doi.org/10.5167/uzh-25168410.1016/j.xgen.2023.100347Test https://www.zora.uzh.ch/id/eprint/251684Test/ https://www.zora.uzh.ch/id/eprint/251684/1/Kleemann_CellGen_2023.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess ; Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ; http://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: | edsbas.C7281C0C |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2666979X |
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| DOI: | 10.5167/uzh-251684 |