Temperature control

A study led by Ludwig Lausanne’s George Coukos, Melita Irving and Fernanda Herrera showed that so-called “cold” tumors that are nearly devoid of immune cells—and therefore unresponsive to immunotherapy—can be turned “hot” with extremely low doses of radiation and the rational use of existing therapies. Researchers have long sought to use high-dose radiation to stimulate anti-tumor immunity, but that is not always an option—for example, when tumors spread into the abdominal cavity, which houses vital organs. To boost the anti-tumor immune responses induced by low-dose irradiation, the researchers combined it with drugs that stimulate dendritic cells, which direct and activate anti-tumor immune responses, and low-dose cyclophosphamide, a chemotherapy that compromises the regulatory T cells that suppress such responses. They also added a combination of anti-CTLA-4 and anti- PD-1 immunotherapies to mobilize a T cell attack on tumors. The researchers reported in Cancer Discovery in September that the combination treatment cured 20% of mice and induced regressions in about a third of eight patients with advanced, immunologically cold cancers. Analysis revealed unusual features in the T cells responsible for the cancer-cell killing as well as the dendritic cells essential to that activity. The findings will be applied to the design of various experimental immunotherapies now being developed at Ludwig Lausanne.

This article appeared in the February 2022 issue of Ludwig Link. Click here to download a PDF (1 MB).


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