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Cited by 341

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Peripheral CD8+ T cell characteristics associated with durable responses to immune checkpoint blockade in patients with metastatic melanoma

Open access
Fairfax, Benjamin P., Taylor, Chelsea A., Watson, Robert A., Nassiri, Isar, Danielli, Sara, Fang, Hai, Mahé, Elise A., Cooper, Rosalin, Woodcock, Victoria, Traill, Zoe, Al-Mossawi, M. Hussein, Knight, Julian C., Klenerman, Paul, Payne, Miranda, Middleton, Mark R.·2020·Nature Medicine

Abstract

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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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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CoChat. (2026). Citation check: Peripheral CD8+ T cell characteristics associated with durable responses to immune checkpoint blockade in patients with metastatic melanoma. https://app.cochat.ai/papers/10.1038/s41591-019-0734-6
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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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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.