The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Cancer-Germline Antigen Expression Discriminates Clinical Outcome to CTLA-4 Blockade
Open accessAbstract
Summary CTLA-4 immune checkpoint blockade is clinically effective in a subset of patients with metastatic melanoma. We identify a subcluster of MAGE-A cancer-germline antigens, located within a narrow 75 kb region of chromosome Xq28, that predicts resistance uniquely to blockade of CTLA-4, but not PD-1. We validate this gene expression signature in an independent anti-CTLA-4-treated cohort and show its specificity to the CTLA-4 pathway with two independent anti-PD-1-treated cohorts. Autophagy, a process critical for optimal anti-cancer immunity, has been previously shown to be suppressed by the MAGE-TRIM28 ubiquitin ligase in vitro. We now show that the expression of the key autophagosome component LC3B and other activators of autophagy are negatively associated with MAGE-A protein levels in human melanomas, including samples from patients with resistance to CTLA-4 blockade. Our findings implicate autophagy suppression in resistance to CTLA-4 blockade in melanoma, suggesting exploitation of autophagy induction for potential therapeutic synergy with CTLA-4 inhibitors.
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Cites
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Cited by
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The hallmarks of successful anticancer immunotherapy
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Self-citationIdentifying and Targeting Human Tumor Antigens for T Cell-Based Immunotherapy of Solid Tumors
Leko, V., & Rosenberg, S. A. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.07.013 · Cited by 449
Genomic correlates of response to immune checkpoint blockade
Keenan, T. E., Burke, K. P., & Van Allen, E. M. (2019) · Nature Medicine · doi:10.1038/s41591-019-0382-x · Cited by 448
Metadata
- Authors
- Shukla, S. A., Bachireddy, P., Schilling, B., Galonska, C., Zhan, Q., Bango, C., Langer, R., Lee, P. C., Gusenleitner, D., Keskin, D. B., Babadi, M., Mohammad, A., Gnirke, A., Clement, K., Cartun, Z. J., Van Allen, E. M., Miao, D., Huang, Y., Snyder, A., Merghoub, T., Wolchok, J. D., Garraway, L. A., Meissner, A., Weber, J. S., Hacohen, N., Neuberg, D., Potts, P. R., Murphy, G. F., Lian, C. G., Schadendorf, D., Hodi, F. S., & Wu, C. J.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 173
- Issue
- 3
- Pages
- 624-633.e8
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2796531277
- Cited by
- 172
- References
- 12
- FWCI
- 6.40
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Shukla, S. A., Bachireddy, P., Schilling, B., Galonska, C., Zhan, Q., Bango, C., Langer, R., Lee, P. C., Gusenleitner, D., Keskin, D. B., Babadi, M., Mohammad, A., Gnirke, A., Clement, K., Cartun, Z. J., Van Allen, E. M., Miao, D., Huang, Y., Snyder, A., . . . Wu, C. J. (2018). Cancer-Germline Antigen Expression Discriminates Clinical Outcome to CTLA-4 Blockade. Cell. https://doi.org/10.1016/j.cell.2018.03.026
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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