The 2018 Nobel Prize in Physiology or Medicine went to James P. Allison and Tasuku Honjo for “their discovery of cancer therapy by inhibition of negative immune regulation”(1). Given the rapidly progressing field of onco-immunotherapy, Dr Stefan’s talk was highly topical and gave a comprehensive overview of existing therapies and their future trajectory. This article hopes to touch on some of the highlights of his talk.

​

Dr Stefan described the ideology behind onco-immunotherapy as treating cancer like a disease that the immune system attacks. However, citing the example of this field where research is flourishing and treatments look promising, Dr Stefan emphasised that scientific discovery is never an individual feat. It’s about a team of people and a network of teams collaborating. He mentioned that popularity in science has a lot to do with reward, but does not necessarily relate to the success of a discovery. For example, everyone knows James Allison – he is popular in his field, he gives lots of talks in English, and he made the CTLA4-inhibitor (which doesn’t really work as Ipilimumab gives a plateau at 20% of patients surviving). However, Tasuku Honjo is not as famous, doesn’t give talks in English, but he discovered the PD1-inhibitor which has a much more potent effect on patient tumours. 

Although immunotherapy has risen to popularity and the public eye quite recently, it has existed since the late twentieth century. The earlier drugs were cytokine modulators, such as BCG (a germ related to tuberculosis bacterium) for bladder cancer. The newer ones include CAR T-cells, where T-cells are cultured outside the body and given to a patient, in a similar way to the old allografts and autografts of solid organs. Today, the recent growing interest in this field was demonstrated by the ASCO 2015 conference, which was dominated by research on immunotherapy.

“I cure no one”, Dr Stefan claimed in his talk, for two reasons. Firstly, to remind us that, despite the hyped success of immunotherapy, the field still has a long way to go; secondly, to highlight that treating people is about giving them not only more time but also a better quality of life. 

A neoantigen is an antigen to which the immune system has not previously been exposed, especially one that arises by alteration of host antigens by viral infection, neoplastic transformation, etc. Currently, it is thought that neoantigens in cancer are the likely to be the most sensitive to immunotherapy and are targets for treatment. Interestingly, PD-1 was the first cancer drug to be approved for tumours regardless of the tumour location: the response rate for tumours with a high mutational load was 50%. In this scenario, mutation load was a better stratified than the tumour site, which was a novel pattern for oncology drug approval. 

Following the success of individual drugs targets at immune checkpoint blockade, such as Ipilimumab (which targets CTLA-4) and Pembrolizumab (which targets PD-1), research was carried out on combining immunotherapies, to see if they can work better together. Results showed that results are better for combined therapies, however toxicity is a problem in this issue. Immunotherapies stimulate the immune system and lead to autoimmunity as an adverse effect. Therefore, it is crucial to identify patients who really need to the combination therapy to prevent