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Single-Cell Profiling of CD8+ T Cells in Acute Myeloid Leukemia Reveals a Continuous Spectrum of Differentiation and Clonal Hyperexpansion

Overview of attention for article published in Cancer Immunology Research, June 2023
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (95th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (54th percentile)

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4 news outlets
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Title
Single-Cell Profiling of CD8+ T Cells in Acute Myeloid Leukemia Reveals a Continuous Spectrum of Differentiation and Clonal Hyperexpansion
Published in
Cancer Immunology Research, June 2023
DOI 10.1158/2326-6066.cir-22-0961
Pubmed ID
Authors

Poonam N. Desai, Bofei Wang, Andre Fonseca, Pamella Borges, Fatima Zahra Jelloul, Patrick K. Reville, Eric Lee, Christopher Ly, Akshay Basi, Jessica Root, Natalia Baran, Sean M. Post, Qing Deng, Hanxiao Sun, Arif O. Harmanci, Jared K. Burks, Javier A. Gomez, Courtney D. DiNardo, Naval G. Daver, Gheath Alatrash, Marina Konopleva, Michael R. Green, Dinler A. Antunes, Andrew Futreal, Dapeng Hao, Hussein A. Abbas

Abstract

Comprehensive investigation of CD8+ T cells in acute myeloid leukemia (AML) is essential for developing immunotherapeutic strategies beyond immune checkpoint blockade. Herein, we performed single-cell RNA profiling of CD8+ T cells from 3 healthy bone marrow donors and 23 newly diagnosed (NewlyDx) and 8 relapsed/refractory (RelRef) AML patients. Cells co-expressing canonical exhaustion markers formed a cluster constituting <1% of all CD8+ T cells. We identified two effector CD8+ T cell subsets characterized by distinct cytokine and metabolic profiles that were differentially enriched in NewlyDx and RelRef patients. We refined a 25-gene CD8-derived signature correlating with therapy resistance, including genes associated with activation, chemoresistance, and terminal differentiation. Pseudotemporal trajectory analysis supported enrichment of a terminally differentiated state in CD8+ T cells with high CD8-derived signature expression at relapse or refractory disease. Higher expression of the 25-gene CD8 AML signature correlated with poorer outcomes in previously untreated AML patients, suggesting that the bona fide state of CD8+ T cells and their degree of differentiation are clinically relevant. Immune clonotype tracking revealed more phenotypic transitions in CD8 clonotypes in NewlyDx than in RelRef patients. Furthermore, CD8+ T cells from RelRef patients had a higher degree of clonal hyperexpansion associated with terminal differentiation and higher CD8-derived signature expression. Clonotype-derived antigen prediction revealed that most previously unreported clonotypes were patient-specific, suggesting significant heterogeneity in AML immunogenicity. Thus, immunologic reconstitution in AML is likely to be most successful at earlier disease stages when CD8+ T cells are less differentiated and have greater capacity for clonotype transitions.

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Attention Score in Context

This research output has an Altmetric Attention Score of 35. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 June 2023.
All research outputs
#1,041,436
of 23,965,413 outputs
Outputs from Cancer Immunology Research
#104
of 1,438 outputs
Outputs of similar age
#9,386
of 197,425 outputs
Outputs of similar age from Cancer Immunology Research
#5
of 11 outputs
Altmetric has tracked 23,965,413 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,438 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.0. This one has done particularly well, scoring higher than 92% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 197,425 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.