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Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer
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 ha...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275757/ https://www.ncbi.nlm.nih.gov/pubmed/32430334 http://dx.doi.org/10.1073/pnas.1922867117 |
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author | Khan, Zia Di Nucci, Flavia Kwan, Antonia Hammer, Christian Mariathasan, Sanjeev Rouilly, Vincent Carroll, Jonathan Fontes, Magnus Ley Acosta, Sergio Guardino, Ellie Chen-Harris, Haiyin Bhangale, Tushar Mellman, Ira Rosenberg, Jonathan Powles, Thomas Hunkapiller, Julie Chandler, G. Scott Albert, Matthew L. |
author_facet | Khan, Zia Di Nucci, Flavia Kwan, Antonia Hammer, Christian Mariathasan, Sanjeev Rouilly, Vincent Carroll, Jonathan Fontes, Magnus Ley Acosta, Sergio Guardino, Ellie Chen-Harris, Haiyin Bhangale, Tushar Mellman, Ira Rosenberg, Jonathan Powles, Thomas Hunkapiller, Julie Chandler, G. Scott Albert, Matthew L. |
author_sort | Khan, Zia |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7275757 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-72757572020-06-11 Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer Khan, Zia Di Nucci, Flavia Kwan, Antonia Hammer, Christian Mariathasan, Sanjeev Rouilly, Vincent Carroll, Jonathan Fontes, Magnus Ley Acosta, Sergio Guardino, Ellie Chen-Harris, Haiyin Bhangale, Tushar Mellman, Ira Rosenberg, Jonathan Powles, Thomas Hunkapiller, Julie Chandler, G. Scott Albert, Matthew L. Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2020-06-02 2020-05-19 /pmc/articles/PMC7275757/ /pubmed/32430334 http://dx.doi.org/10.1073/pnas.1922867117 Text en Copyright © 2020 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Khan, Zia Di Nucci, Flavia Kwan, Antonia Hammer, Christian Mariathasan, Sanjeev Rouilly, Vincent Carroll, Jonathan Fontes, Magnus Ley Acosta, Sergio Guardino, Ellie Chen-Harris, Haiyin Bhangale, Tushar Mellman, Ira Rosenberg, Jonathan Powles, Thomas Hunkapiller, Julie Chandler, G. Scott Albert, Matthew L. Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer |
title | Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer |
title_full | Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer |
title_fullStr | Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer |
title_full_unstemmed | Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer |
title_short | Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer |
title_sort | polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275757/ https://www.ncbi.nlm.nih.gov/pubmed/32430334 http://dx.doi.org/10.1073/pnas.1922867117 |
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