Low-dose radiotherapy to enhance immunotherapy for mesothelioma: characterisation of tumour microenvironment remodelling and treatment optimisation

Abnormal tumour vasculature inhibits the success of cancer treatments. Altering the tumourmicroenvironment could improve treatments and can be achieved through radiotherapy. The doseand fractionation that can best modulate tumours is debated. This study examined the effect ofdifferent radiotherapy dose fractionation schedules on murine mesothelioma models. It was foundthat five fractions of 2 Gy significantly increased tumour blood flow and oxygen saturation in tumoursfor a week post-irradiation. This radiotherapy schedule was then combined with anti-PD-1 and anti-CTLA-4. The combination of treatments significantly improved survival, depending upon the timing oftherapies in relation to each other.