24th January 2017

Lights, Camera, Immuno-action! Research on Cancer Immunotherapy



 

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Melissa Bedard, DPhil in Medical Science (2015)

We all know the classic plot line featured in countless spy and action movies. An intelligence team is defending a country against a foreign enemy or quelling an internal revolution. The team discovers that there is a traitor in their midst, trying to bring the team down from within – an individual who is not only hard to detect, but is also slowly converting others to their side. Only the protagonist can stop the bad guys. While we are familiar with the narrative on the silver screen (who wants to watch The Imitation Game?), did you know that this could happen inside your body?

Here is the star-studded cast of this physiological film: the country – the human body, the traitor – a mutated cell with cancerous potential, the protagonist – your immune cells, specifically your CD8+ T cells and iNKT cells.

Allow me to set the stage: your body is equipped with a specialised system of cells to fight off harmful things, namely infectious foreign agents, in your body – be it the virus that causes your cold, the bacteria that gives you food poisoning, or the fungus that causes your bout of Athlete’s Foot from the gym. This specialised system, the military of the body, is called the immune system, and the individual soldiers/spies are your white blood cells or immune cells. Just as the military has different divisions (navy, air force, etc.), so too does your immune system: dendritic cells, B cells, neutrophils, etc. But let’s focus on two of them: the CD8+ T cells and invariant natural killer (iNKT) cells.

CD8+ T cells can receive intel about the foreign agent by “reading” antigen, a little piece of the agent presented on the surface of infected cells. Based on this intel, the T cells are instructed to kill off the agent. iNKT cells receive intel in a similar manner, but rather than directly eliminate the threat, they coordinate various other immune cells, each equipped with ‘a very particular set of skills’ (as said by Liam Neeson in Taken), to mount a broad, all-encompassing response against the threat.

Now back to the screenplay: immune cells are going about their business, surveying the body for foreign invaders, when suddenly they sense something abnormal. However, it’s not a foreign invader like a virus or bacterium (cue a dramatic Hans Zimmer score), it’s something from your own body! This is how cancer starts; your own normal cells become mutated (due to a combination of genetic and environmental factors) and no longer behave normally. They multiply like crazy and disrupt the proper functioning of the surrounding cells, eventually affecting the tissues, the organ and the organ system as whole. For your immune system, it’s easy to detect a foreign pathogen, as they look very different from your own cells. But in this case, it’s one of your own cells causing harm, and the soldiers of your immune system have been trained not to recognise and kill one of their own!

Cells of your body present little bits of themselves, called self-antigen, on their surface, which immune cells can recognise and conclude that this cell is “self” – thus it is not harmful and not to be attacked. For this reason, even though these cancerous cells are mutating and causing harm, it’s challenging for your immune cells to recognise this harm and mount a response. Furthermore, the cancerous cells that have converted to the ‘dark side’ can evolve to suppress and evade the immune system. How will the immune system defeat this threat from within?

Our lab is trying to better understand the ways in which immune cells recognise and fight cancer cells, and use this knowledge to manipulate immune cells to eliminate cancer in what is termed immunotherapy. While chemotherapy remains a frontline approach to treating cancer, it can have devastating adverse effects on healthy parts of your body and thus be difficult to tolerate. Immunotherapy can boost your own immune cells to very specifically and efficiently target and kill cancer cells. It holds great promise in preventing, treating and eliminating cancer.

The research in our lab focuses on the two types of cells previously described: CD8+ T cells and iNKT cells. We suspect that these are the protagonists who will save the day! We are looking to see if cancer cells, due to their abnormal behaviour, express abnormal protein antigen (called neoantigen) that is different enough from ‘self’ that these CD8+ T cells can recognise the cancer cells, almost as if they were foreign agents, and kill them. Similarly, iNKT cells (the particular focus of my DPhil) recognise different types of antigens derived from lipids (essentially a type of fat), and we think that cancer cells, due to their abnormalities, present different types of lipid antigen – ones that activate iNKT cells and lead to an anti-tumour immune response. An Oscar-worthy performance indeed!

We hope to better understand how CD8+ T cells and iNKT cells fight cancer so that we can further enhance their anti-tumour immune responses and harvest their cancer-killing power in the form of immunotherapy. As well as using our knowledge to treat patients, we hope to develop prophylactic treatment in the form of a cancer vaccine, whereby we could inject cancer-specific antigen (such as neoantigen) to prime the immune system to kill cancerous cells as soon as they arise.

While this plot line might sound exciting as a screenplay, in all seriousness, I’m sure we all, directly or indirectly, understand the plight of those afflicted with cancer. In fact, we in the Teddy Hall community have recently been rallying around a fellow student in the college who has fallen victim to this disease. This sort of personal connection drives our passion for our research and our hope that this work will contribute to preventing, eliminating, or at the very least, greatly improving treatment against cancer.


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