Cancer immunotherapy has been the biggest breakthrough in the treatment of cancer since the advent of chemotherapy. This class of treatments has resulted in survival prognoses going from bleak (&lt;10%) to positive (35-70%) for some of the most devastating tumour types.The approaches generally rely on the activation of tumour specific cytotoxic T-cells through various means such as checkpoint blockade, ex vivo expansion, or vaccination, resulting in the elimination the tumour and all metastases.  One of the great questions in immunology is the mechanism by which these T-cells get activated in the first place. And what determines the success and specificity of the resulting immune response. The natural activators of these T-cells dendritic cells, which activate specific cells by presenting peptides from the tumour for activation. The factors that determine which peptides are presented remain only partially defined.  One major issue here has been the fact that a key step in this peptide presentation is is the proteolytic degradation of the tumour proteome by the dendritic cell. This proteolysis renders all standard labeling methods based on genetic tagging useless, as any polypeptide reporter is destroyed in the process. In my talk, I will present recent work from my group is which we use bioorthogononal labeling strategies to study these processes from start to finish. We use combinations chemistry with flow cytometry, super resolution microscopy and correlative-light electron mircroscopy to map these processes in the dendritic cells. Furthermore, related strategies relying on on-cell deprotection strategies now give us in vivo control over the activation of specific cytotoxic T-cells. With these approaches we aim to unravel what aspects determine which peptide are presented by the dendritic cell driving anti-cancer immunity.

Chemical Immunology - New approaches to study killer T-cell activation

253rd National Meeting (2017)

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