Vitamin feedback loop

Radiotherapy works in large part by stimulating an immune response against cancer cells damaged by ionizing radiation. But that event itself can stimulate the production of factors by tumor cells that suppress those immune responses. A study led by Ludwig Chicago Co-director Ralph Weichselbaum and investigator Hua Laura Liang found that the vitamin A derivative all-trans retinoic acid (RA) helps reprogram the immune microenvironment of tumors and can enhance the effects of radiotherapy in mice. The combination treatment increased the induction within both treated and untreated tumors of inflammatory macrophages. The inflammatory macrophages in turn boosted IFN-γ–producing CD4+ and CD8+ T cells, both of which play critical roles in tumor rejection. The researchers found that these T cells and the IFN-γ they produce feed back into the anti-cancer cascade by further boosting the numbers of inflammatory macrophages in tumors. The researchers reported in Science Immunology in June that the improved therapeutic effects of combining oral ATRA with targeted radiation could be extended to unirradiated tumors in mice with the addition of anti-PD-L1 checkpoint blockade immunotherapy, suggesting a novel and relatively nontoxic intervention to improve treatment outcomes.

This article appeared in the August 2021 issue of Ludwig Link. Click here to download a PDF (2MB).


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