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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 Wang1,2 Connor Lynch1,2 Sean P Pitroda1,2 András Piffkó1,2,3 Kaiting Yang1,2 Amy K Huser1 Hua Laura Liang1,2 Ralph R Weichselbaum1,2

  1. Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USA.
  2. Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.
  3. 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.