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New T cell subsets with potential to improve cellular therapy for cancer identified

Date:
September 14, 2016
Source:
Yale Cancer Center
Summary:
Two genes, NR4A1 and ABC transporters, mark a distinct subset of quiescent T cells within human tissues, researchers say. They report that they have developed methods to mobilize them into circulation for potential application in adoptive T cell therapy of cancer.
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Transfer of human side population T cells into immune-deficient mice leads to greater tissue infiltration compared to unselected T cells.
Credit: Dhodapkar Lab

A Yale Cancer Center research team has identified that two genes, NR4A1 and ABC transporters, mark a distinct subset of quiescent T cells within human tissues, and have developed methods to mobilize them into circulation for potential application in adoptive T cell therapy of cancer.

The study is scheduled for publication on September 12 in the Journal of Clinical Investigation.

Adoptive cellular therapy uses the body's own T cells to boost its immune system to target cancer. The adoptive transfer of T cells has emerged as a promising treatment strategy for cancer, but improvements on enhanced longevity and infiltration to tumor tissue, particularly in solid tumors, are needed.

"Expression of ABC transporters allowed a simple "side population (SP)" assay to detect these cells. Our studies showed that human SP cells were capable of greater engraftment and tissue infiltration than unselected T cells upon adoptive transfer. Further, the finding that these cells could be mobilized into circulation sets the stage for their potential application to improve adoptive T cell therapy," said Madhav V. Dhodapkar, MBBS, Chief of Hematology and the Arthur H. and Isabel Bunker Professor of Hematology at Yale Cancer Center and Smilow Cancer Hospital at Yale New Haven.

"We know that tissue resident memory (Trm) T cells maintain a highly regional network and persist over decades of life with little turnover. The ability to transfer SP cells and create Trm cells to boost the immune system against a patient's cancer could be of therapeutic benefit and needs to be further investigated," explained Dr. Chandra Sekhar Boddupalli, a post-doctoral associate in the Dhodapkar lab and first author of the paper.

Other Yale authors include Shiny Nair, Simon Gray, Rakesh Verma, Joanna Gibson, Clara Abraham, Deepak Narayan, Juan Vasquez, Richard Flavell, Susan Kaech and Kavita Dhodapkar. Heba Nowyhed and Catherine Hedrick from La Jolla Institute for Allergy and Immunology also contributed to the research.


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Materials provided by Yale Cancer Center. Note: Content may be edited for style and length.


Journal Reference:

  1. Chandra Sekhar Boddupalli, Shiny Nair, Simon M. Gray, Heba N. Nowyhed, Rakesh Verma, Joanna A. Gibson, Clara Abraham, Deepak Narayan, Juan Vasquez, Catherine C. Hedrick, Richard A. Flavell, Kavita M. Dhodapkar, Susan M. Kaech, Madhav V. Dhodapkar. ABC transporters and NR4A1 identify a quiescent subset of tissue-resident memory T cells. Journal of Clinical Investigation, 2016; DOI: 10.1172/JCI85329

Cite This Page:

Yale Cancer Center. "New T cell subsets with potential to improve cellular therapy for cancer identified." ScienceDaily. ScienceDaily, 14 September 2016. <www.sciencedaily.com/releases/2016/09/160914172415.htm>.
Yale Cancer Center. (2016, September 14). New T cell subsets with potential to improve cellular therapy for cancer identified. ScienceDaily. Retrieved May 26, 2017 from www.sciencedaily.com/releases/2016/09/160914172415.htm
Yale Cancer Center. "New T cell subsets with potential to improve cellular therapy for cancer identified." ScienceDaily. www.sciencedaily.com/releases/2016/09/160914172415.htm (accessed May 26, 2017).

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