Borrowed resistance

Radiation damages tumors in part by activating an immune response against them. But it has long been thought to also kill T cells, which are essential to that response. This supposition has long been a limiting factor in the use of radiotherapy in trials examining its combination with immunotherapy for the treatment of cancer. A team led by Ludwig Chicago’s Ralph Weichselbaum reported in a September paper in Nature Communications that T cells within tumors might be more resilient than was believed. Ralph and his colleagues found that a large proportion of T cells with some characteristics of tissue resident T cells in irradiated tumors not only survive radiotherapy, but are more activated than T cells from unirradiated tumors and can attack tumors without support from a new infusion of infiltrating T cells. Their analysis indicated that T cells are genetically reprogrammed by the tumor microenvironment to resist radiation, a capability they found to be regulated in part by the factor TGFβ, which is generally thought to be immunosuppressive. The findings suggest that focal irradiation of multiple tumors could improve overall results in combination trials of radio- and immunotherapy.

This article appeared in the November 2019 issue of Ludwig Link. Click here to download a PDF (1 MB).

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