Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma
Top Cited Papers
- 16 February 2018
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 359 (6377), 801-806
- https://doi.org/10.1126/science.aan5951
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. 745Keywords
Funding Information
- National Institutes of Health (K08 CA188615)
- National Institutes of Health (U24CA224316)
- Howard Hughes Medical Institute (Medical Research Fellowship)
- American Association for Cancer Research (KureIt Grant for Kidney Research)
- NIH Office of the Director (P30 CA008748)
- Bristol-Myers Squibb (II-ON Consortium)
- Dana-Farber Cancer Institute (Loker Pinard Funds for Kidney Cancer Research)
- Dana-Farber/Harvard Cancer Center (Kidney SPORE)
- BroadNext10
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