The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1
Open accessAbstract
Human leukocyte antigen (HLA)-independent, T cell–mediated targeting of cancer cells would allow immune destruction of malignancies in all individuals. Here, we use genome-wide CRISPR–Cas9 screening to establish that a T cell receptor (TCR) recognized and killed most human cancer types via the monomorphic MHC class I-related protein, MR1, while remaining inert to noncancerous cells. Unlike mucosal-associated invariant T cells, recognition of target cells by the TCR was independent of bacterial loading. Furthermore, concentration-dependent addition of vitamin B-related metabolite ligands of MR1 reduced TCR recognition of cancer cells, suggesting that recognition occurred via sensing of the cancer metabolome. An MR1-restricted T cell clone mediated in vivo regression of leukemia and conferred enhanced survival of NSG mice. TCR transfer to T cells of patients enabled killing of autologous and nonautologous melanoma. These findings offer opportunities for HLA-independent, pan-cancer, pan-population immunotherapies. Identifying selective tumor-associated molecules that can act as targets for T cells is a major goal of immunotherapy. Sewell and colleagues demonstrate that the nonclassical MHC molecule MR1 is expressed on a wide variety of cancer types and can be targeted by conventional T cells.
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Cites
Improved vectors and genome-wide libraries for CRISPR screening
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Genome-scale CRISPR-Cas9 knockout screening in human cells
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The prognostic landscape of genes and infiltrating immune cells across human cancers
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MR1 presents microbial vitamin B metabolites to MAIT cells
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Self-citationAntimicrobial activity of mucosal-associated invariant T cells
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T-cell activation by transitory neo-antigens derived from distinct microbial pathways
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Self-citationIdentification of essential genes for cancer immunotherapy
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Direct observation of ligand recognition by T cells
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Cited by
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Dissecting esophageal squamous-cell carcinoma ecosystem by single-cell transcriptomic analysis
Zhang, X., Peng, L., Luo, Y., Zhang, S., Pu, Y., Chen, Y., Guo, W., Yao, J., Shao, M., Fan, W., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25539-x · Cited by 363
Dolton, G., Rius, C., Wall, A., Szomolay, B., Bianchi, V., Galloway, S. A. E., Hasan, M. S., Morin, T., Caillaud, M. E., Thomas, H. L., et al. (2023) · Cell · doi:10.1016/j.cell.2023.06.020 · Cited by 153
Self-citationMR1 overexpression correlates with poor clinical prognosis in glioma patients
Kubica, P., Lara-Velazquez, M., Bam, M., Siraj, S., Ong, I., Liu, P., Priya, R., Salamat, S., Brutkiewicz, R. R., & Dey, M. (2021) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdab034 · Cited by 20
Metadata
- Authors
- Crowther, M. D., Dolton, G., Legut, M., Caillaud, M. E., Lloyd, A., Attaf, M., Galloway, S. A. E., Rius, C., Farrell, C. P., Szomolay, B., Ager, A., Parker, A. L., Fuller, A., Donia, M., McCluskey, J., Rossjohn, J., Svane, I. M., Phillips, J. D., & Sewell, A. K.
- Venue
- Nature Immunology
- Published
- 2020-01-20
- Volume
- 21
- Issue
- 2
- Pages
- 178-185
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2998801145
- Cited by
- 267
- References
- 38
- FWCI
- 14.16
- Type
- journal article
- Language
- en
- Open access
- green
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- Crowther, M. D., Dolton, G., Legut, M., Caillaud, M. E., Lloyd, A., Attaf, M., Galloway, S. A. E., Rius, C., Farrell, C. P., Szomolay, B., Ager, A., Parker, A. L., Fuller, A., Donia, M., McCluskey, J., Rossjohn, J., Svane, I. M., Phillips, J. D., & Sewell, A. K. (2020). Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1. Nature Immunology. https://doi.org/10.1038/s41590-019-0578-8
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
