Genetic diversity of tumors with mismatch repair deficiency influences anti–PD-1 immunotherapy response-Reference-Cited by-同舟云学术

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

Published:2019-05-03 Issue:6439 Volume:364 Page:485-491
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Mandal Rajarsi¹²³^ORCID,Samstein Robert M.³⁴^ORCID,Lee Ken-Wing³^ORCID,Havel Jonathan J.³⁵^ORCID,Wang Hao⁶,Krishna Chirag⁷^ORCID,Sabio Erich Y.³,Makarov Vladimir³⁵^ORCID,Kuo Fengshen⁵^ORCID,Blecua Pedro⁴,Ramaswamy Apoorva T.⁸,Durham Jennifer N.²⁶⁹^ORCID,Bartlett Bjarne⁹,Ma Xiaoxiao³^ORCID,Srivastava Raghvendra⁵,Middha Sumit¹⁰^ORCID,Zehir Ahmet¹⁰^ORCID,Hechtman Jaclyn F.¹⁰,Morris Luc GT³⁵¹¹^ORCID,Weinhold Nils⁴,Riaz Nadeem³⁴⁵,Le Dung T.²⁶⁹,Diaz Luis A.⁵¹²^ORCID,Chan Timothy A.³⁴⁵^ORCID

Affiliation:

1. Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins University, Baltimore, MD 21287, USA.

2. Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.

3. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

4. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

5. Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

6. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.

7. Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

8. Department of Otolaryngology–Head and Neck Surgery, Weill Cornell New York Presbyterian Hospital, New York, NY 10065, USA.

9. Swim Across America Laboratory at Johns Hopkins, Baltimore, MD 21287, USA.

10. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

11. Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

12. Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Abstract

High mutational load gets a response 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 et al. studied drivers of differential response to immunotherapy in these patients and found that MSI intensity and insertion-deletion mutations strongly affected therapeutic outcome. Science , this issue p. 485

Funder

National Institutes of Health

Merck

Stand Up To Cancer

Swim Across America

Starr Foundation

Pershing Square Foundation

Conquer Cancer Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary