Understanding the effects of immunomodulatory therapies on radiation response
About the research:
Radiotherapy can ablate tumours through inducing both DNA damage and anti-tumour inflammatory responses. However, innate immunity pathways mounting inflammatory responses can also afford cell intrinsic radioresistance. Work from the Olcina lab has found that one of these innate immunity pathways is the complement system. Targeting complement can modulate anti-tumour immune responses but how to productively harness these to maximise productive inflammation while limiting radioresistance is still unclear. Interestingly, we have recently found that targeting complement receptor C5aR1 can improve tumour radiation response while limiting toxicity to normal tissues in the irradiation field. The protective normal tissue response is associated with decreased apoptosis in the intestinal crypts, a response which is likely dependent on intestinal IL-10-CX3CR1+ macrophages. However, the mechanisms underlying tumour radiation response, including the effects of C5aR1 on anti-tumour immune responses are still poorly understood. To uncover these mechanisms, we will explore the interplay between complement and key innate and adaptive immune components of the tumour microenvironment. These studies will involve the use of co-culture assays as well as in vivo mouse models. Spatial transcriptomics and multiplex imaging will also be employed. The ultimate goal will be to understand how to effectively reprogram the immunosuppressive TME to trigger curative therapeutic radiation responses.
Our group works in a collaborative and multidisciplinary manner. We are interested in a basic to translational approach to science so we collaborate with clinicians and use patient samples or clinical data whenever possible. We also have experience working with in a range of model systems ranging from cell lines to in vivo mouse models. Students can also expect to receive training in bioinformatics and cell and molecular biology techniques. Students will have the opportunity to attend one national and one international conference throughout their DPhil. All members of the lab attend weekly lab meetings which include data presentations, troubleshooting and journal clubs. Dr Olcina meets with students in one-to-one meetings at least once every two weeks.
Olcina MM, Melemenidis S, Nambiar DK, Kim RK, Casey KM, von Eyben R, Woodruff TM, Graves EG, Le QT, Stucki M and Giaccia AJ. bioRxiv. 2020 Oct.
Olcina MM, Balanis NG, Kim RK, Aksoy BA, Kodysh J, Thompson MJ, Hammerbacher J, Graeber TG, Giaccia AJ. Cell Reports. 2018 Dec 26.