دورية أكاديمية
Immune Modulation with RANKL Blockade through Denosumab Treatment in Patients with Cancer.
| العنوان: | Immune Modulation with RANKL Blockade through Denosumab Treatment in Patients with Cancer. |
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| المؤلفون: | Chang H; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California., Marquez J; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California., Chen BK; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California., Kim DM; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California., Cheng ML; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California., Liu EV; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California., Yang H; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California., Zhang L; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California.; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California., Sinha M; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California., Cheung A; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California., Kwek SS; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California., Chow ED; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California.; Department of Biochemistry and Biophysics, Center for Advanced Technologies, University of California San Francisco, San Francisco, California., Bridge M; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California., Aggarwal RR; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California., Friedlander TW; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California., Small EJ; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California., Anderson M; Diabetes Center, Department of Medicine, University of California San Francisco, San Francisco, California., Fong L; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California. |
| المصدر: | Cancer immunology research [Cancer Immunol Res] 2024 Apr 02; Vol. 12 (4), pp. 453-461. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 101614637 Publication Model: Print Cited Medium: Internet ISSN: 2326-6074 (Electronic) Linking ISSN: 23266066 NLM ISO Abbreviation: Cancer Immunol Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Philadelphia, PA : American Association for Cancer Research, [2013]- |
| مواضيع طبية MeSH: | Bone Neoplasms*/drug therapy , Bone Neoplasms*/prevention & control , Bone Neoplasms*/secondary , Denosumab*/therapeutic use, Humans ; Male ; Kidney Neoplasms/drug therapy ; RANK Ligand/antagonists & inhibitors ; Prostatic Neoplasms/drug therapy |
| مستخلص: | Denosumab is a fully human mAb that binds receptor activator of NFκB ligand (RANKL). It is routinely administered to patients with cancer to reduce the incidence of new bone metastasis. RANK-RANKL interactions regulate bone turnover by controlling osteoclast recruitment, development, and activity. However, these interactions also can regulate immune cells including dendritic cells and medullary thymic epithelial cells. Inhibition of the latter results in reduced thymic negative selection of T cells and could enhance the generation of tumor-specific T cells. We examined whether administering denosumab could modify modulate circulating immune cells in patients with cancer. Blood was collected from 23 patients with prostate cancer and 3 patients with renal cell carcinoma, all of whom had advanced disease and were receiving denosumab, prior to and during denosumab treatment. Using high-dimensional mass cytometry, we found that denosumab treatment by itself induced modest effects on circulating immune cell frequency and activation. We also found minimal changes in the circulating T-cell repertoire and the frequency of new thymic emigrants with denosumab treatment. However, when we stratified patients by whether they were receiving chemotherapy and/or steroids, patients receiving these concomitant treatments showed significantly greater immune modulation, including an increase in the frequency of natural killer cells early and classical monocytes later. We also saw broad induction of CTLA-4 and TIM3 expression in circulating lymphocytes and some monocyte populations. These findings suggest that denosumab treatment by itself has modest immunomodulatory effects, but when combined with conventional cancer treatments, can lead to the induction of immunologic checkpoints. See related Spotlight by Nasrollahi and Davar, p. 383. (©2024 The Authors; Published by the American Association for Cancer Research.) |
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| معلومات مُعتمدة: | R35 CA253175 United States CA NCI NIH HHS |
| المشرفين على المادة: | 4EQZ6YO2HI (Denosumab) 0 (RANK Ligand) |
| تواريخ الأحداث: | Date Created: 20240126 Date Completed: 20240403 Latest Revision: 20240408 |
| رمز التحديث: | 20240408 |
| مُعرف محوري في PubMed: | PMC10993769 |
| DOI: | 10.1158/2326-6066.CIR-23-0184 |
| PMID: | 38276989 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2326-6074 |
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| DOI: | 10.1158/2326-6066.CIR-23-0184 |