Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
-
- Naiyer A. Rizvi
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Matthew D. Hellmann
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Alexandra Snyder
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Pia Kvistborg
- Division of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
-
- Vladimir Makarov
- 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.
-
- William Lee
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Jianda Yuan
- Immune Monitoring Core, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Phillip Wong
- Immune Monitoring Core, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Teresa S. Ho
- Immune Monitoring Core, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Martin L. Miller
- Computation Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Natasha Rekhtman
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Andre L. Moreira
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Fawzia Ibrahim
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Cameron Bruggeman
- Department of Mathematics, Columbia University, New York, NY, 10027, USA.
-
- Billel Gasmi
- Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Roberta Zappasodi
- Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Yuka Maeda
- Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Chris Sander
- Computation Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Edward B. Garon
- David Geffen School of Medicine at UCLA, 2825 Santa Monica Boulevard, Suite 200, Santa Monica, CA 90404, USA.
-
- Taha Merghoub
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Jedd D. Wolchok
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
-
- Ton N. Schumacher
- Division of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
-
- Timothy A. Chan
- Weill Cornell Medical College, New York, NY, 10065, USA.
Description
<jats:p>Immune checkpoint inhibitors, which unleash a patient’s own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non–small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors was associated with improved objective response, durable clinical benefit, and progression-free survival. Efficacy also correlated with the molecular smoking signature, higher neoantigen burden, and DNA repair pathway mutations; each factor was also associated with mutation burden. In one responder, neoantigen-specific CD8+ T cell responses paralleled tumor regression, suggesting that anti–PD-1 therapy enhances neoantigen-specific T cell reactivity. Our results suggest that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy.</jats:p>
Journal
-
- Science
-
Science 348 (6230), 124-128, 2015-04-03
American Association for the Advancement of Science (AAAS)
- Tweet
Details 詳細情報について
-
- CRID
- 1361699996082573952
-
- ISSN
- 10959203
- 00368075
-
- Data Source
-
- Crossref