7 Easy Steps to Immune Enlightenment for Oncologists

David J. Kerr, CBE, MD, DSc, FRCP, FMedSci


August 26, 2016

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Hi. I'm David Kerr, professor of cancer medicine from University of Oxford. I did most of my immunology as an undergraduate student about 2.5 thousand years ago. Clearly, all of us practicing medical oncologists are becoming de facto amateur immunologists because of the fantastic insights [we have received] from the therapeutic use of programmed death (PD)-1, PD-L1 inhibitors. All of us are trying to focus on that area, and I'm no different. We have good immunology in Oxford—we've got some fantastic tutors, people I can turn to to explain a few of the details of immunity.

If we can understand the cycle of immunity, we will have insight...for how we might make combination treatments for immune oncology interventions ever more effective.

But recently I read a fantastic review in Annals of Oncology. Doctors Chen and Kim[1] talked about the seven steps to immune escape. Already we have some very gifted immunologists thinking about the escape mechanisms whereby tumors can progress following initial responses to some form of immune intervention, or whether those tumors are de facto resistant right from the beginning. If we can understand the cycle of immunity in molecular and cellular detail, we will have insight not only into immune escape mechanisms, but also for how we might make combination treatments for immune oncology interventions ever more effective.

In the immune cycle we have (1) release of cancer cell antigens, (2) cancer-antigen presentation, (3) priming and activation of T cells, (4) trafficking of T cells to tumors, (5) infiltration of T cells into tumors, (6) recognition of cancer cells by T cells, and (7) eventual killing or destruction of the cancer cells.

Each and every step of the immune cycle has its own set of effector cells [which are met by the tumor with] an increasing recognition of their molecular signals involved in each of these stages. Therefore, the more we understand, the more we'll be able to intervene with some logical combinations [of therapies].

It's a really nice read. I found it entertainingly straightforward in terms of how they took me through the different steps—explaining how things can go wrong, how tumors can evade immune recognition at each and every one of these stages, and how increasingly there is a potential to intervene therapeutically.

At the end of the article, they have a small algorithm pointing towards personalization of immune therapy, by taking a biopsy of the tumor and understanding whether the tumor is inflamed or not inflamed, the degree of activation of T-cell infiltrates, the cytokine environment of the tumor, and even the degree of stromal cells. Dense stroma within the tumor can offer a physical barrier to T-cell infiltration. So, do T cells even get to the right places?

The authors have presented a very logical and relatively easy-to-understand cycle of immunity.

The authors have presented a very logical and relatively easy-to-understand cycle of immunity. I really like that. They broke it down into steps in which they tell us what the key cells and key effective molecules are. They come up with a hypothetical algorithm. And at the end, [they explain] how we might be able to personalize immune treatment in the future by understanding which elements of the immune cycle might be contributing to immune evasion within an individual's cancer.

It's really nice. I really enjoyed reading it and feel better equipped having done so to face the bold, new immune future. I recommend it to you. Have a read and a think. It gives a wee sense of horizon-scanning to where immune oncology might be heading.

Thanks for listening. I'm grateful for any comments you might wish to pose. For the time being, over and out.


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