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Enhanced recruitment of genetically modified CX3CR1-positive human T cells into Fractalkine/CX3CL1 expressing tumors: importance of the chemokine gradient

Overview of attention for article published in Journal for Immunotherapy of Cancer, April 2016
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (88th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (60th percentile)

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1 news outlet
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2 patents

Citations

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79 Dimensions

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81 Mendeley
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Title
Enhanced recruitment of genetically modified CX3CR1-positive human T cells into Fractalkine/CX3CL1 expressing tumors: importance of the chemokine gradient
Published in
Journal for Immunotherapy of Cancer, April 2016
DOI 10.1186/s40425-016-0125-1
Pubmed ID
Authors

Imran Siddiqui, Marco Erreni, Mandy van Brakel, Reno Debets, Paola Allavena

Abstract

Adoptive T-cell based immunotherapies constitute a promising approach to treat cancer, however, a major problem is to obtain effective and long-lasting anti-tumor responses. Lack of response may be due to insufficient trafficking of specific T cells to tumors. A key requirement for efficient migration of cytotoxic T cells is that they express chemokine receptors that match the chemokines produced by tumor or tumor-associated cells. In this study, we investigated whether the in vivo tumor trafficking of activated T cells could be enhanced by the expression of the chemokine receptor CX3CR1. Two human colorectal cancer cell lines were used to set up a xenograft tumor model in immunodeficient mice; the NCI-H630, constitutively expressing the chemokine ligand CX3CL1 (Fractalkine), and the RKO cell line, transduced to express CX3CL1. Human primary T cells were transduced with the receptor CX3CR1-eGFP. Upon in vivo adoptive transfer of genetically modified CX3CR1-T cells in mice bearing NCI-H630 tumors, enhanced lymphocyte migration and tumor trafficking were observed, compared to mice receiving Mock-T cells, indicating improved homing ability towards ligand-expressing tumor cells. Furthermore, significant inhibition of tumor growth was found in mice receiving modified CX3CR1-T cells. In contrast, tumors formed by RKO cells transduced with the ligand (RKO-CX3CL1) were not affected, nor more infiltrated upon transfer of CX3CR1-T lymphocytes, likely because high levels of the chemokine were shed by tumor cells in the systemic circulation, thus nullifying the blood-tissue chemokine gradient. This study demonstrates that ectopic expression of CX3CR1 enhanced the homing of adoptively transferred T cells towards CX3CL1-producing tumors, resulting in increased T cell infiltration in tumor tissues and decreased tumor growth. Our results also establish that a correct chemokine gradient between the systemic circulation and the tumor is an essential requirement in adoptive T-cell based immunotherapy to efficiently recruit T cell effectors at the correct sites.

X Demographics

X Demographics

The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 81 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 81 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 20 25%
Researcher 12 15%
Student > Master 9 11%
Other 6 7%
Student > Doctoral Student 5 6%
Other 9 11%
Unknown 20 25%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 19 23%
Immunology and Microbiology 18 22%
Agricultural and Biological Sciences 8 10%
Medicine and Dentistry 7 9%
Pharmacology, Toxicology and Pharmaceutical Science 3 4%
Other 8 10%
Unknown 18 22%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 16. 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 12 November 2023.
All research outputs
#2,314,773
of 25,374,917 outputs
Outputs from Journal for Immunotherapy of Cancer
#626
of 3,421 outputs
Outputs of similar age
#36,699
of 313,417 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#6
of 15 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,421 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.4. This one has done well, scoring higher than 81% 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 313,417 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 88% of its contemporaries.
We're also able to compare this research output to 15 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 60% of its contemporaries.