Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma-Reference-Cited by-同舟云学术

Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma

Published:2018-02-16 Issue:6377 Volume:359 Page:801-806
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Miao Diana¹²,Margolis Claire A.¹²^ORCID,Gao Wenhua¹^ORCID,Voss Martin H.³⁴^ORCID,Li Wei⁵^ORCID,Martini Dylan J.¹,Norton Craig¹,Bossé Dominick¹^ORCID,Wankowicz Stephanie M.¹²,Cullen Dana⁶,Horak Christine⁶,Wind-Rotolo Megan⁶^ORCID,Tracy Adam²^ORCID,Giannakis Marios¹²,Hodi Frank Stephen¹^ORCID,Drake Charles G.⁷,Ball Mark W.⁸^ORCID,Allaf Mohamad E.⁸^ORCID,Snyder Alexandra³^ORCID,Hellmann Matthew D.³⁴^ORCID,Ho Thai⁹^ORCID,Motzer Robert J.³⁴^ORCID,Signoretti Sabina¹^ORCID,Kaelin William G.¹¹⁰^ORCID,Choueiri Toni K.¹^ORCID,Van Allen Eliezer M.¹²^ORCID

Affiliation:

1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

2. Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA.

3. Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

4. Weill Cornell Medical College, New York, NY 10065, USA.

5. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

6. Bristol-Myers Squibb, New York, NY 10154, USA.

7. Columbia University Medical Center, New York, NY 10032, USA.

8. James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

9. Mayo Clinic, Scottsdale, AZ 85259, USA.

10. Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Abstract

SNF'ing out antitumor immunity Immune checkpoint inhibitors induce durable tumor regressions in some, but not all, cancer patients. Understanding the mechanisms that determine tumor sensitivity to these drugs could potentially expand the number of patients who benefit (see the Perspective by Ghorani and Quezada). Pan et al. discovered that tumor cells in which a specific SWI/SNF chromatin remodeling complex had been experimentally inactivated were more sensitive to T cell–mediated killing. The cells were more responsive to interferon-γ, leading to increased secretion of cytokines that promote antitumor immunity. Miao et al. examined the genomic features of tumors from patients with metastatic renal cell carcinoma who had been treated with immune checkpoint inhibitors. Tumors harboring inactivating mutations in PBRM1 , which encodes a subunit of the same SWI/SNF complex, were more likely to respond to the drugs. Science , this issue p. 770 , p. 801 ; see also p. 745

Funder

National Institutes of Health

Howard Hughes Medical Institute

American Association for Cancer Research

NIH Office of the Director

Bristol-Myers Squibb

Dana-Farber Cancer Institute

Dana-Farber/Harvard Cancer Center

BroadNext10

Publisher

American Association for the Advancement of Science (AAAS)

Subject