Genetic diversity of tumors with mismatch repair deficiency influences anti–PD-1 immunotherapy response

  • Rajarsi Mandal
    Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins University, Baltimore, MD 21287, USA.
  • Robert M. Samstein
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Ken-Wing Lee
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Jonathan J. Havel
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Hao Wang
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
  • Chirag Krishna
    Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Erich Y. Sabio
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Vladimir Makarov
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Fengshen Kuo
    Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Pedro Blecua
    Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Apoorva T. Ramaswamy
    Department of Otolaryngology–Head and Neck Surgery, Weill Cornell New York Presbyterian Hospital, New York, NY 10065, USA.
  • Jennifer N. Durham
    Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
  • Bjarne Bartlett
    Swim Across America Laboratory at Johns Hopkins, Baltimore, MD 21287, USA.
  • Xiaoxiao Ma
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Raghvendra Srivastava
    Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Sumit Middha
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Ahmet Zehir
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Jaclyn F. Hechtman
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Luc GT Morris
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Nils Weinhold
    Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Nadeem Riaz
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Dung T. Le
    Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
  • Luis A. Diaz
    Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Timothy A. Chan
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

書誌事項

公開日
2019-05-03
DOI
  • 10.1126/science.aau0447
公開者
American Association for the Advancement of Science (AAAS)

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説明

<jats:title>High mutational load gets a response</jats:title> <jats:p> Cancers harbor many genetic mutations. Defects in DNA mismatch repair prevent tumors from repairing certain types of DNA damage and lead to a hypermutable genomic state known as microsatellite instability (MSI). Some tumors with a high degree of MSI may be treatable with PD-1 (programmed cell death–1) immunotherapy, but patient response is highly variable. Mandal <jats:italic>et al.</jats:italic> studied drivers of differential response to immunotherapy in these patients and found that MSI intensity and insertion-deletion mutations strongly affected therapeutic outcome. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6439" page="485" related-article-type="in-this-issue" vol="364" xlink:href="10.1126/science.aau0447">485</jats:related-article> </jats:p>

収録刊行物

  • Science

    Science 364 (6439), 485-491, 2019-05-03

    American Association for the Advancement of Science (AAAS)

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