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Understanding the effects of immunomodulatory therapies on radiation response


   Department of Oncology

  ,  Friday, December 09, 2022  Competition Funded PhD Project (Students Worldwide)

About the Project

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 following radiotherapy 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 modes of cell death following complement inhibition. The defence and repair responses mobilised following increased death will be explored, 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 transcriptomics 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

Olcina, M.M., Stavros, M., Nambiar, D.K., Kim, R.K., Casey, K.M., Woodruff, T.M., Graves, E.G., Quynh-Thu, L., Manuel, S. and Giaccia, A.J., 2020. Targeting C5aR1 increases the therapeutic window of radiotherapy. bioRxiv.
Olcina, M.M., Balanis, N.G., Kim, R.K., Aksoy, B.A., Kodysh, J., Thompson, M.J., Hammerbacher, J., Graeber, T.G. and Giaccia, A.J., 2018. Mutations in an innate immunity pathway are associated with poor overall survival outcomes and hypoxic signaling in cancer. Cell reports, 25(13), pp.3721-3732.

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