Skip to 0 minutes and 19 seconds SPEAKER: Understanding the immune signature inside a patient’s tumour is critical if we are to develop new immunotherapies for cancer. Here at the Institute for Translational Medicine in Birmingham, new imaging techniques are being applied to sections of tumors from patients at the Queen Elizabeth Hospital Birmingham, and, in fact, from patient samples from across the UK in order to understand what is going on.
Skip to 0 minutes and 40 seconds CHRIS BAGNALL: Hi, my name is Chris Bagnall. I’m a biomedical scientist attached to the kit grouping. My work is based in the Birmingham HTA Biobank.
Skip to 0 minutes and 48 seconds SPEAKER: The technique Chris is going to be using is called immunohistochemistry, or IHC for short. And it’s quite commonly used in the diagnosis to assess whether a patient is suitable for a drug therapy. But here, Chris is going to be using it to examine the immune signature inside a tumour. Firstly, tumour samples are embedded in wax and cut into thin sections. Then traditionally chemical dyes, or nowadays usually antibodies, would be used to look for the presence of a given molecule in the tumor section. Typically, IHC has looked for the presence of particular markers one at a time.
Skip to 1 minute and 23 seconds However, thanks to support from the QEHB charity, in partnership with the University of Birmingham, we’ve now got some cutting edge technology, the Vectra system from PerkinElmer. It allows us to stain up to six markers on the same piece of tissue. Here we are staining immune cells that do different jobs based on the presence or absence of multiple marker proteins. The Vectra machine also allows us to analyse these colours throughout the slide.
Skip to 1 minute and 49 seconds NEERAJ LAL: Hi. I’m Neeraj Lal. I’m a clinical PhD student working with Professor Wilcox and Professor Middleton. I’m investigating immune signatures in colorectal cancer. And particularly why some patients respond to immunotherapies and why some patients don’t. Staining tumour tissue sections for different markers is important. But equally important is our ability to make sense of the data we get by counting and locating the cells within the tumour sections. Traditionally, for immunohistochemistry, this would have been done by manually counting cells under a microscope. Nowadays we use computers for this, which means we can do this in a semi-automated way. Here we have sophisticated software that can split the tumour sections into different regions.
Skip to 2 minutes and 37 seconds For example, tumour cells, surrounding support structures, and blood vessels, and count the various cell populations within them. We can then analyse how the immune signature relates to patient outcomes and responses to treatment. Here we have a section of colorectal cancer, which has been stained with markers to identify cytotoxic T cells. We then use the computer software to segment the section into tumour and surrounding regions. In orange, we have the tumour itself, and in blue are the surrounding cells. After this step, we ask the software to recognise the cytotoxic T cells. Here you can see it as colouring in the T cells, allowing us to assess how the density relates to patient outcomes.
Skip to 3 minutes and 24 seconds SPEAKER: The technology seen in this video is potentially really significant. It means for the first time we can develop a holistic picture of what the immune response is like in someone’s tumour. We can identify types of immune cells that we previously couldn’t, because we can now co-label them with multiple markers. We can also see geography. In other words, where these different types of immune cells are in relation to one another. This should really push forward our understanding of the immunology of people’s tumours. However, this approach is also potentially really important clinically. Now we know that the immune response in the tumor can be crucial for accurately predicting how quickly a patient’s tumour progresses, particular for certain types of cancer.
Skip to 4 minutes and 6 seconds However, in addition, in the advent of new immunotherapy treatments for cancer, it is very likely that the nature of the immune response within the tumour will be critical in guiding clinicians about which patients respond to a given therapy and which won’t. So the ability to accurately assess the levels and location of the most important immune subsets within the tumour should help us target the right therapy to the right patient.
Studying the immune response inside a tumour
As we mentioned in Week 2, immune cells present within a tumour can sometimes have an effect on cancer progression. In this video Professor Ben Willcox takes you back into the laboratory to meet some researchers who are investigating immune responses inside tumours. They will describe the techniques being used in the laboratory and how the findings can help to develop new treatments.
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