Abscopal effect of radiation therapy: Interplay between radiation dose and p53 status

Lidia Strigari, Mariateresa Mancuso, Valentina Ubertini, Antonella Soriani, Paola Giardullo, Marcello Benassi, Daniela D'Alessio, Simona Leonardi, Silvia Soddu, Gianluca Bossi

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: This study investigates whether the abscopal effect induced by radiation-therapy (RT) is able to sterilize non-irradiated tumour cells through bystander signals. Material and methods: Wild-type (wt)-p53 or p53-null HCT116 human colon cancer cells were xenografted into both flanks of athymic female nude mice. When tumours reached a volume of 0.2 cm3, irradiation was performed, under strict dose monitoring, with a dedicated mobile accelerator designed for intra-Operative-RT (IORT). A dose of 10 or 20 Gy (IR groups), delivered by a 10 MeV electron beam, was delivered to a tumour established in one side flank, leaving the other non-irradiated (NIR groups). A subset of mice were sacrificed early on to carry out short-term molecular analyses. Results: All directly-irradiated tumours, showed a dose-dependent delayed and reduced regrowth, independent of the p53 status. Importantly, a significant effect on tumour-growth inhibition was also demonstrated in NIR wt-p53 tumours in the 20 Gy-irradiation group, with a moderate effect also evident after 10 Gy-irradiation. In contrast, no significant difference was observed in the NIR p53-null tumours, independent of the dose delivered. Molecular analyses indicate that p53-dependent signals might be responsible for the abscopal effect in our model system, via a pro-apoptotic pathway. Conclusions: We suggest that the interplay between delivered dose and p53 status might help to sterilize out-of-field tumour cells.

Original languageEnglish
Pages (from-to)248-255
Number of pages8
JournalInternational Journal of Radiation Biology
Volume90
Issue number3
DOIs
Publication statusPublished - Mar 2014

Keywords

  • Apoptosis
  • In vivo abscopal effect
  • IORT
  • P53
  • Tumour growth

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

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