The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance
Open accessAbstract
SUMMARY Clinically acquired resistance to MAPK inhibitor (MAPKi) therapies for melanoma cannot be fully explained by genomic mechanisms and may be accompanied by co-evolution of intra-tumoral immunity. We sought to discover non-genomic mechanisms of acquired resistance and dynamic immune compositions by a comparative, transcriptomic-methylomic analysis of patient-matched melanoma tumors biopsied before therapy and during disease progression. Transcriptomic alterations across resistant tumors were highly recurrent, in contrast to mutations, and were frequently correlated with differential methylation of tumor cell-intrinsic CpG sites. We identified in the tumor cell compartment supra-physiologic c-MET up-expression, infra-physiologic LEF1 down-expression, and YAP1 signature enrichment as drivers of acquired resistance. Importantly, high intra-tumoral cytolytic T-cell inflammation prior to MAPKi therapy preceded CD8 T-cell deficiency/exhaustion and loss of antigen-presentation in half of disease-progressive melanomas, suggesting cross-resistance to salvage anti-PD-1/PD-L1 immunotherapy. Thus, melanoma acquires MAPKi-resistance with highly dynamic and recurrent non-genomic alterations and co-evolving intra-tumoral immunity.
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Citations
Cites
1 retracted
Host immunity contributes to the anti-melanoma activity of BRAF inhibitors
Knight, D. A., Ngiow, S. F., Li, M., Parmenter, T., Mok, S., Cass, A., Haynes, N. M., Kinross, K., Yagita, H., Koya, R. C., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66236 · Cited by 269
Self-citationRetractedMolecular and genetic properties of tumors associated with local immune cytolytic activity
Rooney, M. S., Shukla, S. A., Wu, C. J., Getz, G., & Hacohen, N. (2015) · Cell · doi:10.1016/j.cell.2014.12.033 · Cited by 3,825
Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer
Twyman-Saint Victor, C., Rech, A. J., Maity, A., Rengan, R., Pauken, K. E., Stelekati, E., Benci, J. L., Xu, B., Dada, H., Odorizzi, P. M., et al. (2015) · Nature · doi:10.1038/nature14292 · Cited by 2,434
Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
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Self-citationCombined Vemurafenib and Cobimetinib in BRAF -Mutated Melanoma
Larkin, J., Ascierto, P. A., Dréno, B., Atkinson, V., Liszkay, G., Maio, M., Mandalà, M., Demidov, L., Stroyakovskiy, D., Thomas, L., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408868 · Cited by 2,068
Self-citationCombined BRAF and MEK Inhibition versus BRAF Inhibition Alone in Melanoma
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Self-citationTumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion
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Self-citationCOT drives resistance to RAF inhibition through MAP kinase pathway reactivation
Johannessen, C. M., Boehm, J. S., Kim, S. Y., Thomas, S. R., Wardwell, L., Johnson, L. A., Emery, C. M., Stransky, N., Cogdill, A. P., Barretina, J., et al. (2010) · Nature · doi:10.1038/nature09627 · Cited by 1,460
PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors
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Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling
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Cited by
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Tirosh, I., Izar, B., Prakadan, S. M., Wadsworth, M. H., Treacy, D., Trombetta, J. J., Rotem, A., Rodman, C., Lian, C., Murphy, G., et al. (2016) · Science · doi:10.1126/science.aad0501 · Cited by 4,944
Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma
Hugo, W., Zaretsky, J. M., Sun, L., Song, C., Moreno, B. H., Hu-Lieskovan, S., Berent-Maoz, B., Pang, J., Chmielowski, B., Cherry, G., et al. (2016) · Cell · doi:10.1016/j.cell.2016.02.065 · Cited by 3,448
Self-citationThe immune contexture in cancer prognosis and treatment
Fridman, W. H., Zitvogel, L., Sautès–Fridman, C., & Kroemer, G. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.101 · Cited by 2,263
A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade
Jerby-Arnon, L., Shah, P., Cuoco, M. S., Rodman, C., Su, M.-J., Melms, J. C., Leeson, R., Kanodia, A., Mei, S., Lin, J.-R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.006 · Cited by 1,429
Mechanisms of resistance to immune checkpoint inhibitors
Jenkins, R. W., Barbie, D. A., & Flaherty, K. T. (2018) · British Journal of Cancer · doi:10.1038/bjc.2017.434 · Cited by 1,383
Metadata
- Authors
- Hugo, W., Shi, H., Sun, L., Piva, M., Song, C., Kong, X., Moriceau, G., Hong, A., Dahlman, K. B., Johnson, D. B., Sosman, J. A., Ribas, A., & Lo, R. S.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 162
- Issue
- 6
- Pages
- 1271-1285
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1834835434
- Cited by
- 600
- References
- 32
- FWCI
- 22.13
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hugo, W., Shi, H., Sun, L., Piva, M., Song, C., Kong, X., Moriceau, G., Hong, A., Dahlman, K. B., Johnson, D. B., Sosman, J. A., Ribas, A., & Lo, R. S. (2015). Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance. Cell. https://doi.org/10.1016/j.cell.2015.07.061
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