Investigators: Raelene Endersby, Nick Gottardo, Jacqueline Whitehouse, Meegan Howlett, Jessica Buck, Mathew Ancliffe, Courtney George, Zahra Abbas, Mani Kuchibhotla
Project description
Medulloblastoma and high-grade glioma are among the most common paediatric brain cancers. In recent years, immunotherapy has emerged as a promising adjunct to conventional therapy, yet functional characteristics of the immune microenvironment and activation of specific immune populations in these cancers remains relatively unknown. Using flow cytometry and multicolour immunofluorescence microscopy, we explore the immune microenvironment of these cancers in pre-clinical models. We also evaluate the changes to immune cell infiltration following conventional cytotoxic therapy and radiation therapy. Our data demonstrate that the most abundant immune cell in these cancers are microglia - innate immune cells and the resident macrophages of the brain.
In this project, we we also seek to evaluate the effectiveness of several different immunotherapies in these cancers. We are studying a new therapy that disrupts the CD47-SIRPalpha axis between innate immune cells and cancer cells, also known as the "don't eat me" axis. We are examining the anti-cancer effects of antibody treatment in combination with conventional chemotherapy and radiation therapy in our laboratory models. Also, we are examining the ability of genetically-modified T cells to attack brain cancers. These studies will provide insight to the viability of current immunotherapies for these cancers, and guide the application of novel therapeutic agents to improve outcomes for these children.
Collaborators
- Terrance Johns
- Siddartha Mitra
- Geoff McCowage
- Belinda Kramer
- Misty Jenkins
- Jason Waithman
- Joost Lesterhuis
Partners
- The Kids Cancer Project
- Love for Lachie
- Tour de Cure
- Pirate Ship Foundation
- Ethan Davies Foundation