The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
Developmental Relationships of Four Exhausted CD8+ T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms
Open accessAbstract
SUMMARY CD8+ T cell exhaustion is a major barrier to current anti-cancer immunotherapies. Despite this, the developmental biology of exhausted CD8+ T cells (Tex) remains poorly defined, restraining improvement of strategies aimed at “re-invigorating” Tex cells. Here, we defined a four-cell-stage developmental framework for Tex cells. Two TCF1+ progenitor subsets were identified, one tissue restricted and quiescent and one more blood accessible, that gradually lost TCF1 as it divided and converted to a third intermediate Tex subset. This intermediate subset re-engaged some effector biology and increased upon PD-L1 blockade but ultimately converted into a fourth, terminally exhausted subset. By using transcriptional and epigenetic analyses, we identified the control mechanisms underlying subset transitions and defined a key interplay between TCF1, T-bet, and Tox in the process. These data reveal a four-stage developmental hierarchy for Tex cells and define the molecular, transcriptional, and epigenetic mechanisms that could provide opportunities to improve cancer immunotherapy.
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Metadata
- Authors
- Beltra, J.-C., Manne, S., Abdel-Hakeem, M. S., Kurachi, M., Giles, J. R., Chen, Z., Casella, V., Ngiow, S. F., Khan, O., Huang, Y. J., Yan, P., Nzingha, K., Xu, W., Amaravadi, R. K., Xu, X., Karakousis, G. C., Mitchell, T. C., Schuchter, L. M., Huang, A. C., & Wherry, E. J.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2020-05
- Volume
- 52
- Issue
- 5
- Pages
- 825-841.e8
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W3020888809
- Cited by
- 1,082
- References
- 69
- FWCI
- 34.10
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Beltra, J.-C., Manne, S., Abdel-Hakeem, M. S., Kurachi, M., Giles, J. R., Chen, Z., Casella, V., Ngiow, S. F., Khan, O., Huang, Y. J., Yan, P., Nzingha, K., Xu, W., Amaravadi, R. K., Xu, X., Karakousis, G. C., Mitchell, T. C., Schuchter, L. M., Huang, A. C., & Wherry, E. J. (2020). Developmental Relationships of Four Exhausted CD8+ T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms. Immunity. https://doi.org/10.1016/j.immuni.2020.04.014
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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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