Study uncovers inhibitory role of 'Ter cells' in cancer therapies

25 Feb 2021
Study uncovers inhibitory role of 'Ter cells' in cancer therapies

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 tumour progression.

The study focused on Ter cells, which are extra medullary erythroid precursors that secrete the neuropeptide artemin.

In the study, published in Science Translational Medicine, the researchers showed that local tumour radiotherapy, systemic immunotherapy or the combination of both treatments were able to deplete Ter cells in the spleen, reduce artemin production and limit tumour progression both in the locally irradiated tumours 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 signalling, and immunotherapy, according to the authors, led to enhanced control of tumour 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 signalling 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 tumour-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 tumour-promoting pathways."

Source: University of Chicago Medical Center