دورية أكاديمية
Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients.
| العنوان: | Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients. |
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| المؤلفون: | Mathew D; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Marmarelis ME; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Foley C; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Bauml JM; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Ye D; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Ghinnagow R; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Ngiow SF; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Klapholz M; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Jun S; Department of Radiation Oncology and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA., Zhang Z; Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA, USA., Zorc R; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Davis CW; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Diehn M; Department of Radiation Oncology and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA., Giles JR; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Huang AC; Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Hwang WT; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Zhang NR; Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA, USA., Schoenfeld AJ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Carpenter EL; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Langer CJ; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Wherry EJ; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Minn AJ; Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. |
| المصدر: | Science (New York, N.Y.) [Science] 2024 Jun 21; Vol. 384 (6702), pp. eadf1329. Date of Electronic Publication: 2024 Jun 21. |
| نوع المنشور: | Journal Article; Clinical Trial, Phase II |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Original Publication: New York, N.Y. : [s.n.] 1880- |
| مواضيع طبية MeSH: | Carcinoma, Non-Small-Cell Lung*/drug therapy , Carcinoma, Non-Small-Cell Lung*/immunology , Carcinoma, Non-Small-Cell Lung*/therapy , CD8-Positive T-Lymphocytes*/immunology , Immune Checkpoint Inhibitors*/therapeutic use , Janus Kinase 1*/antagonists & inhibitors , Janus Kinase Inhibitors*/therapeutic use , Lung Neoplasms*/drug therapy , Lung Neoplasms*/immunology , Lung Neoplasms*/therapy , Programmed Cell Death 1 Receptor*/antagonists & inhibitors, Animals ; Female ; Humans ; Mice ; Immunotherapy/methods |
| مستخلص: | Persistent inflammation driven by cytokines such as type-one interferon (IFN-I) can cause immunosuppression. We show that administration of the Janus kinase 1 (JAK1) inhibitor itacitinib after anti-PD-1 (programmed cell death protein 1) immunotherapy improves immune function and antitumor responses in mice and results in high response rates (67%) in a phase 2 clinical trial for metastatic non-small cell lung cancer. Patients who failed to respond to initial anti-PD-1 immunotherapy but responded after addition of itacitinib had multiple features of poor immune function to anti-PD-1 alone that improved after JAK inhibition. Itacitinib promoted CD8 T cell plasticity and therapeutic responses of exhausted and effector memory-like T cell clonotypes. Patients with persistent inflammation refractory to itacitinib showed progressive CD8 T cell terminal differentiation and progressive disease. Thus, JAK inhibition may improve the efficacy of anti-PD-1 immunotherapy by pivoting T cell differentiation dynamics. |
| التعليقات: | Comment in: Science. 2024 Jun 21;384(6702):1303-1304. doi: 10.1126/science.adq1717. (PMID: 38900897) |
| معلومات مُعتمدة: | P01 CA210944 United States CA NCI NIH HHS; R01 AI115712 United States AI NIAID NIH HHS; U19 AI082630 United States AI NIAID NIH HHS |
| المشرفين على المادة: | 0 (Immune Checkpoint Inhibitors) EC 2.7.10.2 (JAK1 protein, human) EC 2.7.10.2 (Janus Kinase 1) 0 (Janus Kinase Inhibitors) 0 (PDCD1 protein, human) 0 (Programmed Cell Death 1 Receptor) |
| تواريخ الأحداث: | Date Created: 20240620 Date Completed: 20240620 Latest Revision: 20240704 |
| رمز التحديث: | 20240704 |
| DOI: | 10.1126/science.adf1329 |
| PMID: | 38900877 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1095-9203 |
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| DOI: | 10.1126/science.adf1329 |