Immunobiology of Brain Tumours
The dialogue between cancer and the immune response is complex and can have unique features according to the site of growth of a solid tumour. Our group focuses on brain tumours, particularly gliomas, and their interaction with spontaneous and induced immune responses.
We are intensively investigating a novel tumour vaccine that is based on antigenic proteins coupled to a cell penetrating peptide (CPP) that is efficiently delivered to antigen presenting cells. This leads to efficient processing and presentation of antigenic peptides to both CD4 and CD8 T cells. To have therapeutic impact, vaccine-induced T cells much reach the tumour and function in the tumour bed. We have identified markers and mechanisms by which T cells are programmed to efficiently traffic to a brain tumour; the optimal vaccine will exploit these properties. Stimulation of protective CD4 T cells is as important as stimulating CD8 cytotoxic T cells. In mouse brain tumour models (and in human glioma), the balance is towards regulatory CD4 T cells and an immunosuppressive tumour microenvironment, whereas transfer of Th1 polarised CD4 T cells can promote CD8 T cell recruitment and type 1 cytokine secretion.
Ultimately, the immune cells that impact on tumour growth must function in the hostile tumour bed that often has a low oxygen tension; we are therefore exploring immune function under hypoxia to better understand this tumour microenvironment. Finally, clinical translation of cancer immunotherapy will generally require compatibility with other treatments previously or concomitantly given to patients. Our research objective is to identify chemotherapies that can synergise with immunotherapy to target even glioma stem-like cells that are refractory to current treatment modalities.