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Response to Immunotherapy in Patients With ‘Claudin-Low’ Breast Tumors

Posted: Tuesday, September 12, 2017

A team of investigators at the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center may have an explanation for why some aggressive breast tumors do not respond to immunotherapy, and it seems to center on the protein claudin. They found that “claudin-low” triple-negative breast tumors had an elevated level of immune cells in and around the tumors, which seemed to prevent the immune system from being effective. These research findings were published in the Journal of Clinical Investigation.

“It’s important for us to try to start segregating out the types of tumors that don’t respond to these treatments at a much granular genomic level and try to figure out new mechanisms to enhance the response rate to immunotherapy,” said the study’s senior author Jonathan Serody, MD, Elizabeth Thomas Professor of the UNC School of Medicine, in a press release.

To improve the effectiveness of immune-stimulating cancer treatments, Dr. Serody and colleagues tested an investigational approach to stringently deplete the regulatory T cells and combined the treatment with a checkpoint inhibitor. With this strategy, tumor growth was impaired and survival prolonged, although it was insufficient to mediate tumor regression. The authors concluded that targeting the immunosuppressive environment generated by the tumor in combination with checkpoint inhibition should be the focus of future clinical trials.