Radiotherapy and immunology

The majority of cancer patients receive radiotherapy during the course of treatment, delivered with curative intent for local tumor control or as part of a multimodality regimen aimed at eliminating distant metastasis. A major focus of research has been DNA damage; however, in the past two decades, emphasis has shifted to the important role the immune system plays in radiotherapy-induced anti-tumor effects. Radiotherapy reprograms the tumor microenvironment, triggering DNA and RNA sensing cascades that activate innate immunity and ultimately enhance adaptive immunity. In opposition, radiotherapy also induces suppression of anti-tumor immunity, including recruitment of regulatory T cells, myeloid-derived suppressor cells, and suppressive macrophages. The balance of pro- and anti-tumor immunity is regulated in part by radiotherapy-induced chemokines and cytokines. Microbiota can also influence radiotherapy outcomes and is under clinical investigation. Blockade of the PD-1/PD-L1 axis and CTLA-4 has been extensively investigated in combination with radiotherapy; we include a review of clinical trials involving inhibition of these immune checkpoints and radiotherapy.

Liangliang Wang^1,2 Connor Lynch^1,2 Sean P Pitroda^1,2 András Piffkó^1,2,3 Kaiting Yang^1,2 Amy K Huser¹ Hua Laura Liang^1,2 Ralph R Weichselbaum^1,2

Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USA.
Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.
Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Source: Liangliang Wang, Connor Lynch, Sean P Pitroda et al. Radiotherapy and immunology. J Exp Med. 2024 Jul 1;221(7):e20232101. doi: 10.1084/jem.20232101.

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