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Skip to 0 minutes and 14 seconds SPEAKER 1: This graph enables us to think about how the level of changes in achievement compared to normal cells or mutations varies across different humans and different patients. Each patient is represented by a dot, with increasing levels of changes plotted higher up the curve. Patients have been grouped according to tumour, with the tumours arranged left-to-right, in order of increasing levels of changes. In the previous video, we mentioned that checkpoint blockade is able to unleash responses to mutated bits of the tumour. Here, we would like you to consider four questions. Firstly, checkpoint blockade has being relatively successful in melanoma, a type of skin cancer, and also in lung cancer, both highlighted in green towards the right-hand side of the plot.

Skip to 1 minute and 2 seconds Does this fit with our idea that, in these tumours, this therapy works because it unleashes responses to changed or mutated targets?

Skip to 1 minute and 15 seconds Secondly, in contrast, checkpoint blockade has been relatively unsuccessful in prostate cancer, highlighted here in red in the middle of the plot. Why do you think this might be the case?

Skip to 1 minute and 36 seconds Thirdly, what do you notice about the differences between different patients– different dots– within a particular tumour type? As an example, look at colorectal cancer, highlighted here. In this patient group, some patients respond– shown in green– and others tend not to, shown in red. How can you explain the different responses? Could differences in the level of changed or mutated targets explain why some people respond to checkpoint blockade?

Skip to 2 minutes and 11 seconds Finally, choose a different tumour and have a think whether this therapy is likely to work. For example, stomach cancer, head and neck cancer, renal cancer, liver cancer, or brain cancer– such as glioma or glioblastoma.

How does mutation in a tumour affect the success of checkpoint blockade therapy?

Watch the video presented by Professor Ben Willcox. As you watch, consider how the level of changes or mutations in a particular tumour can affect the response of a patient to checkpoint blockade therapy.

The questions in the video are included in the discussion Step 3.9, where you can post your answers and/or comments to compare your thoughts with other learners.

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This video is from the free online course:

Cancer Immunotherapy: a Step Change in Cancer Treatment

University of Birmingham