Modulating the tumour microenvironment using low dose radiotherapy to improve immunotherapy efficacy in mesothelioma

Synat Keam

Research output: ThesisDoctoral Thesis

157 Downloads (Pure)

Abstract

The currently FDA approved nivolumab and ipilimumab combination is effective only in small subset of mesothelioma patients. Therefore, improved therapy is required. Here, I showed low dose radiotherapy fractionation (2 Gy × 5 fractions) transiently remodelled tumour vasculature characterised by increased vascular perfusion and reduced tumour hypoxia. This radiotherapy dose also enhanced intra-tumoural CD8+ T cell infiltration and increased gene expression associated with immunologically “hot” tumour characteristics. The combination of this radiotherapy fractionation withaPD-1/aCTLA-4 cured 100% of mesothelioma bearing mice. My finding may guide the design of radio-immunotherapy clinical trial in the next couple of years.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • The University of Western Australia
Supervisors/Advisors
  • Cook, Alistair, Supervisor
  • Nowak, Anna, Supervisor
  • Ebert, Martin, Supervisor
Thesis sponsors
Award date13 Mar 2023
DOIs
Publication statusUnpublished - 2022

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