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[Music] Our task at Roche is to find ways to help our immune system fight not only infections, but to enhance it so it can also fight cancer — and our research has given us the understanding and opportunity to do exactly that. Recent research into cancer immunotherapy and human immune biology has led to two innovative approaches to treating cancer from the Roche Research and Development teams.
One of these exciting approaches is the ability to understand how best to separate all human cancers — of which there are over 200 known types — into just three primary immune profiles.
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We refer to these profiles as:
Inflamed tumors
Immune-excluded tumors
Immune deserts
When thinking about these profiles, we like to think of an army of immune cells, also known as T-cells. When the tumor is inflamed, it has an army of T-cells armed and ready to attack the cancer from inside the castle grounds of the tumor. We call the castle grounds the tumor microenvironment.
When the tumor is described as immune-excluded, you can imagine the T-cell army is ready to attack but is unable to scale the walls or cross the moat of the castle to attack effectively.
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Finally, the immune desert is exactly as it sounds — there is a tumor, but no T-cell army is present to mount an attack.
Now, the importance of understanding this biology is that we can start to be very specific about what we are trying to do in any person that presents with one of these immune profiles. This allows us to apply different treatment strategies to target the individual immune biology, ensuring that the individual has the best chance of a response to a specific treatment.
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We now understand that by using this vital information — together with another approach to personalizing treatments — we can target specific immune biologies even further.
The cancer immunity cycle is a framework that my friend and colleague Dan Chen and I devised, which helps to describe how a tumor interacts with the immune system. We've broken that down into seven major steps. Here's Dan to explain the seven steps:
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The cancer immunity cycle is a framework that helps to describe how a tumor interacts with the human immune system.
Step 1: This is where cancer cells die and release antigens — protein bits of themselves.
Step 2: Those protein bits can get picked up by antigen-presenting cells, such as dendritic cells, which migrate to local draining lymph nodes.
Step 3: In the lymph nodes, those antigen-presenting cells can present the cancer protein bits to T-cells. When functioning correctly, these T-cells become activated against those proteins.
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Step 4: Activated T-cells enter the bloodstream and circulate throughout the body, searching for tumor deposits.
Step 5: T-cells arrive at the tumor site and must now infiltrate the tumor by exiting the blood vessels and entering the tumor microenvironment.
Step 6: Within the microenvironment, T-cells must recognize cancer cells. T-cells are highly specific and will look for their target protein bits on the surface of cancer cells.
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Step 7: Once the T-cell recognizes a cancer cell, it must kill it. This step is critical. However, many inhibitory factors can block a T-cell from effectively killing cancer cells.
Blocking PD-L1 or other inhibitory signals may help those activated T-cells do their job. And once they succeed in killing a cancer cell, the cycle restarts.
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So now that we understand the cancer immunity cycle, we can ask:
Whom do you give a cancer immunotherapy to?
Which therapy is most likely to achieve the best results for an individual patient?
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Armed with this level of knowledge — and a detailed map of potential treatments and pathways — we are now able to target specific steps of the cancer immunity cycle. This helps our own bodies fight cancer, and takes us a step closer to personalizing cancer immunotherapy for individual tumors and people.
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