RIG-I immunotherapy overcomes radioresistance in p53-positive malignant melanoma

S Lambing, YP Tan, P Vasileiadou, S Holdenrieder, P Mueller, C Hagen, S Garbe, R Behrendt, M Schlee, JG van den Boorn, E Bartok, M Renn, G Hartmann

Research output: Contribution to journalA1: Web of Science-articlepeer-review


Radiotherapy induces DNA damage, resulting in cell cycle arrest and activation of cell-intrinsic death pathways. However, the radioresistance of some tumour entities such as malignant melanoma limits its clinical application. The innate immune sensing receptor retinoic acid-inducible gene I (RIG-I) is ubiquitously expressed and upon activation triggers an immunogenic form of cell death in a variety of tumour cell types including melanoma. To date, the potential of RIG-I ligands to overcome radioresistance of tumour cells has not been investigated. Here, we demonstrate that RIG-I activation enhanced the extent and immunogenicity of irradiation-induced tumour cell death in human and murine melanoma cells in vitro and improved survival in the murine B16 melanoma model in vivo. Transcriptome analysis pointed to a central role for p53, which was confirmed using p53–/– B16 cells. In vivo, the additional effect of RIG-I in combination with irradiation on tumour growth was absent in mice carrying p53–/– B16 tumours, while the antitumoural response to RIG-I stimulation alone was maintained. Our results identify p53 as a pivotal checkpoint that is triggered by RIG-I resulting in enhanced irradiation-induced tumour cell death. Thus, the combined administration of RIG-I ligands and radiotherapy is a promising approach to treating radioresistant tumours with a functional p53 pathway, such as melanoma.
Original languageEnglish
Article numbermjad001
JournalJournal of Molecular Cell Biology
Issue number1
Number of pages14
Publication statusPublished - 2023


  • RIG-I
  • Immunotherapy
  • Irradiation
  • Melanoma
  • P53
  • Radioresistance
  • Radiotherapy


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