Understanding how to effectively reprogram the immunosuppressive tumour microenvironment to improve tumour responses while limiting toxicity

Primary Supervisor: Dr Monica Olcina

Project Overview

Dying cancer cells are thought to be a rich source of tumour antigens and danger signals into the tumour microenvironment. Work from the Olcina lab has found that targeting complement can increase tumour cell death within the tumour microenvironment which may in turn modulate anti-tumour immune responses. However, how to productively harness these responses to maximise productive inflammation while limiting normal tissue toxicity is still unclear. To uncover these mechanisms, we will explore the defence and repair responses mobilised following increased death, including their impact on key innate and adaptive immune responses in the tumour microenvironment. These studies will involve the use of cell and molecular biology techniques as well as in vivo mouse models. Flow cytometry, analysis of spatial omics and multiplex imaging will also be undertaken. The ultimate goal will be to understand how to effectively reprogram the immunosuppressive tumour microenvironment to trigger curative therapeutic responses.

References

Beach, C., MacLean, D., Majorova, D., Melemenidis, S., Nambiar, D.K., Kim, R.K., Valbuena, G.N., Guglietta, S., Krieg, C., Darvish-Damavandi, M. and Suwa, T., 2024. Improving radiotherapy in immunosuppressive microenvironments by targeting complement receptor C5aR1. The Journal of clinical investigation, 133(23).

https://www.jci.org/articles/view/168277