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Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade
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epigenetic landscape. These data indicate that epigenetic fate inflexibility may limit current immunotherapies.
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“However, whether the epigenetic landscape of the tumor cells or T cell exhaustion is contributing to resistance is not well understood, leaving much room for further understanding of how epigenetics can lead to nonresponse to ICIs (108, 109).”
From Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance (2021) · cites this paper as [109]
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Clinical implications of T cell exhaustion for cancer immunotherapy
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“Consistent with the notion that lack of epigenetic plasticity limits the reversal of T cell exhaustion, TEX do not develop into memory T cells (TMEM) after PD-1 blockade but instead re-exhaust (Pauken et al., 2016).”
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“To assess whether H3K9Ac correlated with chromatin accessibility, we compared our observed differential enrichment against a previously reported gene list of effector and exhaustion datasets generated by ATAC-seq analysis in T cells after chronic antigen stimulation (37).”
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“Elegant work from Wherry and colleagues showed that PD-1/PD-L1 checkpoint blockade had minimal sustained impact on the transcriptional and epigenetic characteristics of exhausted CD8 T cells arising during chronic LCMV infection: although these reinvigorated cells showed re-induction of effector programs that improved…”
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Metadata
- Authors
- Pauken, K. E., Sammons, M. A., Odorizzi, P. M., Manne, S., Godec, J., Khan, O., Drake, A. M., Chen, Z., Sen, D. R., Kurachi, M., Barnitz, R. A., Bartman, C., Bengsch, B., Huang, A. C., Schenkel, J. M., Vahedi, G., Haining, W. N., Berger, S. L., & Wherry, E. J.
- Affiliations
- University of Pennsylvania (US)
- Harvard University (US)
- Dana-Farber Cancer Institute (US)
- University of Minnesota (US)
- Broad Institute (US)
- Corresponding author
- Wherry, E. John
- ORCID
- Venue
- Science
- Published
- 2016-12-02
- Volume
- 354
- Issue
- 6316
- Pages
- 1160-1165
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5484795
- OpenAlex
- W2541574334
- Cited by
- 1,348
- References
- 37
- Citations by year
- 2026: 162 · 2025: 128 · 2024: 122 · 2023: 160 · 2022: 145 · 2021: 166 · 2020: 162 · 2019: 129 · 2018: 106 · 2017: 66 · 2016: 2
- FWCI
- 54.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Robertson Foundation–Cancer Research Institute Irvington Fellowship
- American Cancer Society Postdoctoral Fellowship
- German Research Foundation Fellowship (BE5496/1-1)
- National Institutes of Health (F30DK100159, T32 2T32CA009615-26, CA78831, AI105343, AI112521, AI082630, AI115712, AI117950, AI108545)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- exhausted T cells, epigenetic stability, anti-PD-1 therapy, T cell reinvigoration, T cell exhaustion
- MeSH terms
- Animals, Female, Immunologic Memory, Immunotherapy, Mice, Inbred C57BL, Transcription, Genetic, Interleukin-7, CD8-Positive T-Lymphocytes, Cell Lineage, Epigenesis, Genetic, Mice, Gene Regulatory Networks, B7-H1 Antigen, Cellular Reprogramming
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