What can T-cells see on human cancer?
Prof Ton Schumacher – The Netherlands Cancer Institute, Amsterdam, The Netherlands
I was here at the WIN Symposium to discuss our work on neo-antigens, mutant epitopes that occur in human cancers and this can be recognised by the immune system. What we are seeing is that in patients that respond to immunotherapy that a T-cell based immune system can generally see these variant epitopes on cancer cells as being foreign and react to them.
What is a neo-antigen and why is it important in relation to human cancer?
The main base to be interested in this work is that we now know that cancer immunotherapies can be highly active within the clinic. We do not really know what these T-cells that mediate these effects need to see on the cancer cells in order to be able to kill them. In our work we’re testing the hypothesis that what these T-cells see is mutant epitopes, variant epitopes, that arise as a consequence of the DNA mutations within the cancer cells.
What is some of the research you have been doing in the area?
Most of our research over the past few years we have focussed on melanoma patients treated with different types of immunotherapy, either cellular therapy or checkpoint blockades. In those patients we’ve analysed how frequently the immune system recognises these mutant epitopes on the cancer cells. What we see is that in most of the patients there is an immune response against these mutant epitopes that occur within the cancer.
What is the aim of your research, what do you hope to achieve?
I think with our current work and work from Steve Rosenberg at NIH it is now quite clear the recognition of these mutant epitopes is a very important ingredient of cancer immunotherapy. That really sets us up for the next stage where we try to specifically enhance immune reactivity against these variant epitopes so there will be a form of personalised cancer immunotherapy.
Why have you chosen to focus on melanoma?
Most of this research has been done in melanoma because traditionally we had the biggest hope immunotherapy would work in melanoma. We actually now also know that immunotherapy can be active in tumours such as bladder cancer, lung cancer, head and neck cancers and actually also in some of those tumour types we do see evidence that the immune system reacts to these kinds of mutant epitopes. So we’re now slowly moving away from melanoma towards these other tumour types.
What about combining immunotherapy with other forms of therapy such as chemotherapy and radiotherapy?
I think there’s a strong rationale to do that. One rationale actually looking at our work would be that the traditional therapies could serve as a way to alert the immune system to what’s on the cancer cells by liberating antigens. So synergy with checkpoint blockade is something that may potentially occur, I think that deserves to be tested. In addition it’s going to be really important to test whether we can develop more targeted strategies to really induce immune reactivity against mutant epitopes on cancer cells.
Any other points from your presentation that you would like to highlight?
At this point in time it is quite clear that immunotherapy, this reactivity, is of significant importance. It would be quite nice to also test whether in targeted therapies or classical chemotherapy actually the immune system also plays a significant role. On the basis of the work that has emerged over the past few years this is likely to be the case in at least some patients.
Do you have a final take home message from your presentation?
The final take home message from our work is that the immune system has evolved to fight an enemy that evolves through time, pathogens. One of the issues in cancer therapy has been that tumours also have a tendency to adapt. The immune system actually is a very nice way to deal with the adaptation.
