Regulatory T Cells Shape the Differential Impact of Radiation Dose-Fractionation Schedules on Host Innate and Adaptive Antitumor Immune Defenses
Joseph Sia, Jim Hagekyriakou, Ioana Chindris, Hassan Albarakati, Trevor Leong, Ramona Schlenker, Simon P Keam, Scott G Williams, Paul J Neeson, Ricky W Johnstone, Nicole M Haynes
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | ELSEVIER SCIENCE INC | Published : 2021
PURPOSE: We examined how radiation dose per fraction (DPF) and total dose, as represented by biological effective dose (BED), can independently and differentially affect the immunomodulatory capacity of radiation therapy (RT). METHODS AND MATERIALS: AT3-OVA mammary and MC38 colorectal tumors in C57BL/6 mice were irradiated with rationally selected dose-fractionation schedules, alone or with immune-modulating or -depleting agents. Tumor growth was monitored as a readout of therapeutic response. Flow cytometry and RNA sequencing of mouse tumors and analysis of transcriptomic data sets from irradiated human cancers were used to examine the immunomodulatory effects of the different radiation sch..View full abstract
Work from the Johnstone laboratory was supported by the imCORE Network on behalf of F. Hoffmann-La Roche Ltd (R.W.J. and N.M.H.) , the Cancer Council Victoria, National Health and Medical Research Council of Australia (NHMRC) and The Kids' Cancer Project (R.W.J.) , the II-ON network on behalf of Bristol Myers Squibb (N.M.H.) , the Australian Government Research Training Program Scholarship and the Royal Aus-tralian New Zealand College of Radiologists (RANZCR) Withers and Peters Grant (J.S.) .