The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Peripheral CD8+ T cell characteristics associated with durable responses to immune checkpoint blockade in patients with metastatic melanoma
Open accessAbstract
Immune checkpoint blockade (ICB) of PD-1 and CTLA-4 to treat metastatic melanoma (MM) has variable therapeutic benefit. To explore this in peripheral samples, we characterized CD8+ T cell gene expression across a cohort of patients with MM receiving anti-PD-1 alone (sICB) or in combination with anti-CTLA-4 (cICB). Whereas CD8+ transcriptional responses to sICB and cICB involve a shared gene set, the magnitude of cICB response is over fourfold greater, with preferential induction of mitosis- and interferon-related genes. Early samples from patients with durable clinical benefit demonstrated overexpression of T cell receptor–encoding genes. By mapping T cell receptor clonality, we find that responding patients have more large clones (those occupying >0.5% of repertoire) post-treatment than non-responding patients or controls, and this correlates with effector memory T cell percentage. Single-cell RNA-sequencing of eight post-treatment samples demonstrates that large clones overexpress genes implicated in cytotoxicity and characteristic of effector memory T cells, including CCL4, GNLY and NKG7. The 6-month clinical response to ICB in patients with MM is associated with the large CD8+ T cell clone count 21 d after treatment and agnostic to clonal specificity, suggesting that post-ICB peripheral CD8+ clonality can provide information regarding long-term treatment response and, potentially, facilitate treatment stratification. Transcriptomic analysis of peripheral CD8+ T cells in a cohort of patients with metastatic melanoma receiving checkpoint inhibitors shows that the number of large clones early post-treatment is strongly associated with six-month clinical outcome.
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A blood atlas of COVID-19 defines hallmarks of disease severity and specificity
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Self-citation
Metadata
- Authors
- Fairfax, B. P., Taylor, C. A., Watson, R. A., Nassiri, I., Danielli, S., Fang, H., Mahé, E. A., Cooper, R., Woodcock, V., Traill, Z., Al-Mossawi, M. H., Knight, J. C., Klenerman, P., Payne, M., & Middleton, M. R.
- Venue
- Nature Medicine
- Published
- 2020-02
- Volume
- 26
- Issue
- 2
- Pages
- 193-199
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W3005134677
- Cited by
- 341
- References
- 42
- FWCI
- 15.96
- Type
- journal article
- Language
- en
- Open access
- green
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- Fairfax, B. P., Taylor, C. A., Watson, R. A., Nassiri, I., Danielli, S., Fang, H., Mahé, E. A., Cooper, R., Woodcock, V., Traill, Z., Al-Mossawi, M. H., Knight, J. C., Klenerman, P., Payne, M., & Middleton, M. R. (2020). Peripheral CD8+ T cell characteristics associated with durable responses to immune checkpoint blockade in patients with metastatic melanoma. Nature Medicine. https://doi.org/10.1038/s41591-019-0734-6
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