Research ArticleIMMUNOTHERAPY

All-trans retinoic acid overcomes solid tumor radioresistance by inducing inflammatory macrophages

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Science Immunology  11 Jun 2021:
Vol. 6, Issue 60, eaba8426
DOI: 10.1126/sciimmunol.aba8426

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Radiosensitizer recipe for tumors

Cancer radiotherapy stimulates immunogenic cell death of tumor cells, thereby boosting antitumor T cell immunity. However, cancer radiotherapy simultaneously elicits local production and recruitment of immunosuppressive molecules and cells. Rao et al. investigated combining oral all-trans retinoic acid (ATRA) with tumor irradiation in mouse cancer models as a means of reprogramming intratumoral myeloid cells and enhancing systemic antitumor immunity. Supplementing radiotherapy with a course of ATRA increased the induction of inflammatory macrophages and IFN-γ–producing CD4+ and CD8+ T cells within tumors. ATRA-assisted reprogramming of the tumor microenvironment promoted local and systemic T cell–mediated effects on tumors including abscopal effects on distal nonirradiated tumors. These findings provide a rationale for designing human clinical trials to test ATRA as a radiosensitizer to boost antitumor T cell responses after radiation therapy.

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