The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma
Open accessAbstract
PD-1 immune checkpoint blockade provides significant clinical benefits for melanoma patients. We analyzed the somatic mutanomes and transcriptomes of pretreatment melanoma biopsies to identify factors that may influence innate sensitivity or resistance to anti-PD-1 therapy. We find that overall high mutational loads associate with improved survival, and tumors from responding patients are enriched for mutations in the DNA repair gene BRCA2. Innately resistant tumors display a transcriptional signature (referred to as the IPRES, or innate anti-PD-1 resistance), indicating concurrent up-expression of genes involved in the regulation of mesenchymal transition, cell adhesion, extracellular matrix remodeling, angiogenesis, and wound healing. Notably, mitogen-activated protein kinase (MAPK)-targeted therapy (MAPK inhibitor) induces similar signatures in melanoma, suggesting that a non-genomic form of MAPK inhibitor resistance mediates cross-resistance to anti-PD-1 therapy. Validation of the IPRES in other independent tumor cohorts defines a transcriptomic subset across distinct types of advanced cancer. These findings suggest that attenuating the biological processes that underlie IPRES may improve anti-PD-1 response in melanoma and other cancer types.
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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
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PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
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GSVA: gene set variation analysis for microarray and RNA-Seq data
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Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
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PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377
Comprehensive molecular characterization of human colon and rectal cancer
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Cancer immunotherapy using checkpoint blockade
Ribas, A., & Wolchok, J. D. (2018) · Science · doi:10.1126/science.aar4060 · Cited by 6,791
Self-citationMismatch repair deficiency predicts response of solid tumors to PD-1 blockade
Le, D. T., Durham, J. N., Smith, K. N., Wang, H., Bartlett, B. R., Aulakh, L. K., Lu, S., Kemberling, H., Wilt, C., Luber, B. S., et al. (2017) · Science · doi:10.1126/science.aan6733 · Cited by 6,645
The Immune Landscape of Cancer
Thorsson, V., Gibbs, D. L., Brown, S. D., Wolf, D., Bortone, D. S., Ou Yang, T.-H., Porta-Pardo, E., Gao, G. F., Plaisier, C. L., Eddy, J. A., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.023 · Cited by 5,870
Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy
Sharma, P., Hu-Lieskovan, S., Wargo, J. A., & Ribas, A. (2017) · Cell · doi:10.1016/j.cell.2017.01.017 · Cited by 5,588
Self-citationTGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells
Mariathasan, S., Turley, S. J., Nickles, D., Castiglioni, A., Yuen, K., Wang, Y., Kadel III, E. E., Koeppen, H., Astarita, J. L., Cubas, R., et al. (2018) · Nature · doi:10.1038/nature25501 · Cited by 5,400
Metadata
- Authors
- Hugo, W., Zaretsky, J. M., Sun, L., Song, C., Moreno, B. H., Hu-Lieskovan, S., Berent-Maoz, B., Pang, J., Chmielowski, B., Cherry, G., Seja, E., Lomeli, S., Kong, X., Kelley, M. C., Sosman, J. A., Johnson, D. B., Ribas, A., & Lo, R. S.
- Affiliations
- University of California, Los Angeles (US)
- Vanderbilt University (US)
- Corresponding author
- Lo, Roger S.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 165
- Issue
- 1
- Pages
- 35-44
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4808437
- OpenAlex
- W2299181842
- Cited by
- 3,448
- References
- 46
- Citations by year
- 2026: 175 · 2025: 281 · 2024: 370 · 2023: 409 · 2022: 478 · 2021: 461 · 2020: 406 · 2019: 316 · 2018: 268 · 2017: 205 · 2016: 70
- FWCI
- 153.57
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-01-26)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (UL1TR000124)
- National Cancer Institute (P01CA168585, K12 CA 0906525, K12CA090625, R35CA197633, P30CA016042, R01CA176111)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- metastatic melanoma, anti-PD-1 therapy, immune checkpoint blockade, treatment response prediction, BRCA2 mutation, non-specific immunity, mesenchymal transition, extracellular matrix remodeling, angiogenesis, MAPK inhibitor resistance, cross-resistance, tumor transcriptome
- MeSH terms
- Nivolumab, Antibodies, Monoclonal, Antineoplastic Agents, Humans, Melanoma, Neoplasm Metastasis, Drug Resistance, Neoplasm, MAP Kinase Signaling System, BRCA2 Protein, Transcriptome, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized
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