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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia
|
|---|---|
| Published in |
Nature Medicine, April 2018
|
| DOI | 10.1038/s41591-018-0010-1 |
| Pubmed ID | |
| Authors |
Joseph A. Fraietta, Simon F. Lacey, Elena J. Orlando, Iulian Pruteanu-Malinici, Mercy Gohil, Stefan Lundh, Alina C. Boesteanu, Yan Wang, Roddy S. O’Connor, Wei-Ting Hwang, Edward Pequignot, David E. Ambrose, Changfeng Zhang, Nicholas Wilcox, Felipe Bedoya, Corin Dorfmeier, Fang Chen, Lifeng Tian, Harit Parakandi, Minnal Gupta, Regina M. Young, F. Brad Johnson, Irina Kulikovskaya, Li Liu, Jun Xu, Sadik H. Kassim, Megan M. Davis, Bruce L. Levine, Noelle V. Frey, Donald L. Siegel, Alexander C. Huang, E. John Wherry, Hans Bitter, Jennifer L. Brogdon, David L. Porter, Carl H. June, J. Joseph Melenhorst |
| Abstract |
Tolerance to self-antigens prevents the elimination of cancer by the immune system1,2. We used synthetic chimeric antigen receptors (CARs) to overcome immunological tolerance and mediate tumor rejection in patients with chronic lymphocytic leukemia (CLL). Remission was induced in a subset of subjects, but most did not respond. Comprehensive assessment of patient-derived CAR T cells to identify mechanisms of therapeutic success and failure has not been explored. We performed genomic, phenotypic and functional evaluations to identify determinants of response. Transcriptomic profiling revealed that CAR T cells from complete-responding patients with CLL were enriched in memory-related genes, including IL-6/STAT3 signatures, whereas T cells from nonresponders upregulated programs involved in effector differentiation, glycolysis, exhaustion and apoptosis. Sustained remission was associated with an elevated frequency of CD27+CD45RO-CD8+ T cells before CAR T cell generation, and these lymphocytes possessed memory-like characteristics. Highly functional CAR T cells from patients produced STAT3-related cytokines, and serum IL-6 correlated with CAR T cell expansion. IL-6/STAT3 blockade diminished CAR T cell proliferation. Furthermore, a mechanistically relevant population of CD27+PD-1-CD8+ CAR T cells expressing high levels of the IL-6 receptor predicts therapeutic response and is responsible for tumor control. These findings uncover new features of CAR T cell biology and underscore the potential of using pretreatment biomarkers of response to advance immunotherapies. |
X Demographics
The data shown below were collected from the profiles of 150 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 50 | 33% |
| Spain | 6 | 4% |
| Australia | 5 | 3% |
| Mexico | 3 | 2% |
| France | 3 | 2% |
| Turkey | 2 | 1% |
| Singapore | 2 | 1% |
| Norway | 2 | 1% |
| Russia | 2 | 1% |
| Other | 22 | 15% |
| Unknown | 53 | 35% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 91 | 61% |
| Scientists | 45 | 30% |
| Practitioners (doctors, other healthcare professionals) | 10 | 7% |
| Science communicators (journalists, bloggers, editors) | 4 | 3% |
Mendeley readers
The data shown below were compiled from readership statistics for 1,157 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1157 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 224 | 19% |
| Student > Ph. D. Student | 183 | 16% |
| Other | 91 | 8% |
| Student > Bachelor | 87 | 8% |
| Student > Master | 84 | 7% |
| Other | 137 | 12% |
| Unknown | 351 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 223 | 19% |
| Immunology and Microbiology | 171 | 15% |
| Medicine and Dentistry | 157 | 14% |
| Agricultural and Biological Sciences | 104 | 9% |
| Pharmacology, Toxicology and Pharmaceutical Science | 28 | 2% |
| Other | 98 | 8% |
| Unknown | 376 | 32% |
Attention Score in Context
This research output has an Altmetric Attention Score of 241. 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 09 April 2024.
All research outputs
#158,642
of 25,734,859 outputs
Outputs from Nature Medicine
#687
of 9,412 outputs
Outputs of similar age
#3,640
of 339,506 outputs
Outputs of similar age from Nature Medicine
#17
of 89 outputs
Altmetric has tracked 25,734,859 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 9,412 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 105.8. 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 339,506 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 98% of its contemporaries.
We're also able to compare this research output to 89 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.