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Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma
Open accessAbstract
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
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“Hypoxia can directly upregulate the expression of various cellular immune checkpoints (such as programmed cell death‐ligand 1, PD‐L1) in the TME.”
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Metadata
- Authors
- Miao, D., Margolis, C. A., Gao, W., Voss, M. H., Li, W., Martini, D. J., Norton, C., Bossé, D., Wankowicz, S. M., Cullen, D., Horak, C., Wind-Rotolo, M., Tracy, A., Giannakis, M., Hodi, F. S., Drake, C. G., Ball, M. W., Allaf, M. E., Snyder, A., Hellmann, M. D., Ho, T., Motzer, R. J., Signoretti, S., Kaelin, W. G., Choueiri, T. K., & Van Allen, E. M.
- Affiliations
- Broad Institute (US)
- Dana-Farber Cancer Institute (US)
- Memorial Sloan Kettering Cancer Center (US)
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
- Bristol-Myers Squibb (United States) (US)
- Bristol-Myers Squibb, New York, NY 10154, USA.
- Columbia University Irving Medical Center (US)
- Johns Hopkins University (US)
- Mayo Clinic in Arizona (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Choueiri, Toni K.
- ORCID
- Miao, Diana
- Margolis, Claire A.
- Gao, Wenhua
- Voss, Martin H.
- Li, Wei
- Martini, Dylan J.
- Bossé, Dominick
- Wind-Rotolo, Megan
- Tracy, Adam
- Giannakis, Marios
- Hodi, Frank Stephen
- Drake, Charles G.
- Ball, Mark W.
- Allaf, Mohamad E.
- Snyder, Alexandra
- Hellmann, Matthew D.
- Ho, Thai
- Motzer, Robert J.
- Signoretti, Sabina
- Kaelin, William G.
- Choueiri, Toni K.
- Van Allen, Eliezer M.
- Venue
- Science
- Published
- 2018-02-16
- Volume
- 359
- Issue
- 6377
- Pages
- 801-806
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6035749
- OpenAlex
- W2782183686
- Cited by
- 1,249
- References
- 57
- Citations by year
- 2026: 73 · 2025: 93 · 2024: 153 · 2023: 164 · 2022: 186 · 2021: 195 · 2020: 179 · 2019: 113 · 2018: 89
- FWCI
- 54.48
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (K08 CA188615, 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
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
- Keywords
- clear cell renal cell carcinoma, immune checkpoint inhibitors, SWI/SNF complex, PBRM1 mutation, tumor response prediction, antitumor immunity, interferon-gamma, T cell-mediated killing, metastatic renal cell carcinoma, cancer genomics
- MeSH terms
- Carcinoma, Renal Cell, Chromosomal Proteins, Non-Histone, Humans, Immunotherapy, Kidney Neoplasms, Mutation, Transcription Factors, Cohort Studies, Gene Expression Profiling, Genomics, Exome, B7-H1 Antigen, CTLA-4 Antigen, Programmed Cell Death 1 Receptor
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