Plenary lecture: T cell recognition in human cancer – Ton Schumacher, Netherlands Cancer Institute, The Netherlands

09:45-10:25

Room: Hall 1A

Many human tumors contain large numbers of mutations, of which many hundreds can be present within expressed genes. As the resulting altered protein sequences are foreign to the immune system, immune recognition of such ‘neo-antigens’ has been proposed as a major factor in the activity of clinically used immunotherapeutics such as anti-CTLA-4 and anti-PD-1. In support of this hypothesis, work by others and us has over the past years demonstrated that CD4 and CD8 T cell recognition of the consequences of DNA damage is a common feature in, e.g., human melanoma, and can also be boosted by immunotherapy. These data establish ‘tumor foreignness’, as determined by neo-antigen formation, as one of the determinants of effective cancer immunotherapies. However, it is evident that the outcome of cancer – immune interaction is also critically dependent on a number of other factors. With the ultimate aim to describe a ‘cancer – immunogram’ that depicts the state of cancer – immune interactions for individual patients, we are developing and exploiting genetic screens and (functional) assays of human tumor material. A detailed understanding of the specific bottleneck(s) in immune-mediated tumor control in individual patients should be of value for both patient selection and for the development of novel clinical interventions.