Skip to 0 minutes and 13 seconds INSTRUCTOR: In some of the last videos, we’ve told you that checkpoint blockade therapies can remove the brakes on the immune response, unleashing a strong immune attack against a tumour. But in our second week, we emphasised that attacking tumour cells is often a real challenge for the immune system, because tumours are caused by uncontrolled growth of our own cells, whereas the immune system is mainly concerned with recognising signs of foreign invaders. So what, then, is the immune system actually recognising on cancer cells when we use these checkpoint blockade therapies to create a strong attack on the tumour?
Skip to 0 minutes and 47 seconds Well, if you remember back to our previous video on what is cancer, we mentioned towards the end that cancer cells do have changes to their DNA called mutations that distinguish them from normal cells. Well, the current evidence suggests that when checkpoint blockade works, it may well be these mutations in the form of mutated protein fragments which are often being recognised by T cells that are unleashed in a tumour. Let’s have a look at how that works. Inside the cancer cells, the mutated DNA results in production mutated proteins, fragments of which are displayed on the cell surface by the specialised MHC proteins we mentioned earlier.
Skip to 1 minute and 29 seconds And because these fragments contain mutations compared to normal proteins, they are recognised as different by T cells. And we think is T cell responses against these kind of mutated targets, displayed in the context of MHC proteins, that are unleashed in checkpoint blockade therapy. In a way, this is a really interesting case where the success of the therapy– in this case, checkpoint blockade– has helped teach the immunologist what is going on. And it reminds us immunologists of what the whole point of the immune system is– to recognise the difference in normality– in other words, recognition of non-self. Mostly, this means foreign invaders. But in the case of cancer, this can be mutated proteins.
Skip to 2 minutes and 13 seconds So this idea could lead us to make a prediction. We could predict that those cancers that are most mutated, that have most differences in their proteins from normal cells, will be the ones that also look pretty different to the immune system– i.e. the ones that are most like non-self. If this prediction is true, these cancers should generate the biggest immune responses and stand the best chance of benefiting from checkpoint blockade therapy to unleash that response. In the next task, we will ask you to do a little bit of investigation to find out if this is true.
Cancer as 'non-self' – immune responses to cancer mutations
In this video, Professor Ben Willcox helps us to consider how the immune system can distinguish cancer cells from normal cells, which is the key to the success of checkpoint blockade therapy.
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