Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer
| العنوان: | Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer |
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| المؤلفون: | Magnus Fontes, Sergio Ley Acosta, Ellie Guardino, Sanjeev Mariathasan, Matthew L. Albert, Vincent Rouilly, Christian Hammer, G. Scott Chandler, Jonathan Rosenberg, J. D. Carroll, Ira Mellman, Antonia Kwan, Tushar Bhangale, Haiyin Chen-Harris, Julie Hunkapiller, Thomas Powles, Zia Khan, F. Di Nucci |
| المصدر: | Proceedings of the National Academy of Sciences. 117:12288-12294 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Oncology, medicine.medical_specialty, Multidisciplinary, Bladder cancer, business.industry, Cancer, Atopic dermatitis, Vitiligo, medicine.disease, Immune checkpoint, Atezolizumab, Psoriasis, Internal medicine, Medicine, Adverse effect, business, Cancer immunology |
| الوصف: | PD-1 and PD-L1 act to restrict T-cell responses in cancer and contribute to self-tolerance. Consistent with this role, PD-1 checkpoint inhibitors have been associated with immune-related adverse events (irAEs), immune toxicities thought to be autoimmune in origin. Analyses of dermatological irAEs have identified an association with improved overall survival (OS) following anti-PD-(L)1 therapy, but the factors that contribute to this relationship are poorly understood. We collected germline whole genome sequencing data from IMvigor211, a recent phase 3 randomized controlled trial comparing atezolizumab (anti-PD-L1) monotherapy to chemotherapy in bladder cancer. We found that high vitiligo, high psoriasis, and low atopic dermatitis polygenic risk scores (PRSs) were associated with longer OS under anti-PD-L1 monotherapy as compared to chemotherapy, reflecting the Th17 polarization of these diseases. PRSs were not correlated with tumor mutation burden, PD-L1 immunohistochemistry, nor T-effector gene signatures. Shared genetic factors impact risk for dermatological autoimmunity and anti-PD-L1 monotherapy in bladder cancer. |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::14f7a18fa18e8a42336818349d0d4293Test https://doi.org/10.1073/pnas.1922867117Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....14f7a18fa18e8a42336818349d0d4293 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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