University of Chicago study uncovers inhibitory role of ‘Ter cells’ in cancer therapies

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Results identify multiple targets to potentially improve outcomes after radiotherapy and immunotherapy.

Targeted radiation is often used to study and treat diverse cancer types. A multidisciplinary research team based at the University of Chicago Medicine has recently focused on a type of cell that releases a protein that enhances resistance to cancer therapies and promotes tumor progression.

The study focused on Ter cells, which are extra medullary erythroid precursers that secrete the neuropeptide artemin. In the study, published February 24, 2020, in Science Translational Medicine, the researchers showed that local tumor radiotherapy, systemic immunotherapy or the combination of both treatments were able to deplete Ter cells in the spleen, reduce artemin production and limit tumor progression both in the locally irradiated tumors as well as outside the radiation fields.

The results identified several targets that could “potentially improve outcomes after radio- and immunotherapy,” said Ralph Weichselbaum, MD, Daniel K. Ludwig Distinguished Service Professor and chair of radiation and cellular oncology at the University of Chicago. “The promise of these approaches is exciting.”

This study used animal models and samples from three different groups of patients who had received some combination of radiotherapy and chemotherapy, immunotherapy and radio-immunotherapy respectively for various forms of cancer, including lung cancer and melanoma.

Combinations of Ter cell depletion, blockade of artemin signaling, and immunotherapy, according to the authors, led to enhanced control of tumor burden in mice. Ter cell depletion, the authors noted, was dependent on an intact adaptive immune response, mediated by interferon-y.

Targeting the Ter artemin axis “enhanced the efficacy of immunotherapy in model systems,” Weichselbaum said. Reduced numbers of Ter cells and reduced expression of artemin and artemin signaling partners were all associated with improved outcomes in patients receiving radiotherapy, radioimmunotherapy and immunotherapy.

“Together, our study demonstrates the mutually apposing regulatory effects between radiotherapy or immunotherapy and tumor-induced splenic Ter cells,” the authors suggest.

These immunotherapies and combined treatments with radiotherapy, according to the authors, “warrant further research to understand the interactions between them and tumor-promoting pathways.”

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“Radiotherapy and immunotherapy converge on elimination of tumor-promoting erythoid progenitor cells through adaptive immunity” was published February 24, 2020, in Science Translational Medicine. Additional authors are Y. Hou of Xi’an Jiaotong University and Ludwig Center for Metastasis Research at the University of Chicago; Xinshuang Yu of First Affiliated Hospital of Shandong; Zhida Liu, Xuezhi Cao and Yang-Xin Fu of University of Texas Southwest Medical Center; Enyu Rao of Xuzhou Medical University; Wenjun Wu of Fox Chase Cancer Center, Philadelphia; Sean Z. Luo of Whitney Young High School, Chicago; and H.L. Liang, Xiaona Huang, Liangliang Wang, Lei Li, Jason Bugno, Yanbin Fu, Steven Chmura, Wenxin Zheng, Ainhoa Arina, Jessica Jutzy, Anne R. McCall, Everett Vokes and Sean Pitroda of the University of Chicago.

About the University of Chicago Medicine & Biological Sciences

The University of Chicago Medicine, with a history dating back to 1927, is one of the nation’s leading academic health systems. It unites the missions of the University of Chicago Medical Center, Pritzker School of Medicine and the Biological Sciences Division. Twelve Nobel Prize winners in physiology or medicine have been affiliated with the University of Chicago Medicine. Its main Hyde Park campus is home to the Center for Care and Discovery, Bernard Mitchell Hospital, Comer Children’s Hospital and the Duchossois Center for Advanced Medicine. It also has ambulatory facilities in Orland Park, South Loop and River East as well as affiliations and partnerships that create a regional network of care. UChicago Medicine offers a full range of specialty-care services for adults and children through more than 40 institutes and centers including an NCI-designated Comprehensive Cancer Center. Together with Harvey-based Ingalls Memorial, UChicago Medicine has 1,296 licensed beds, nearly 1,300 attending physicians, over 2,800 nurses and about 970 residents and fellows.

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Alison Caldwell
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http://dx.doi.org/10.1126/scitranslmed.abb0130

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