Immunotherapy of hepatocellular carcinoma

Published on July 31, 2017 Archived on June 29, 2023   43 min

Other Talks in the Series: Immunotherapy of Cancer

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My name is Tim Greten, I'm a senior investigator at the National Cancer Institute in Bethesda, Maryland, and I'm going to give you a presentation entitled Immunotherapy of Hepatocellular Carcinoma.
Hepatocellular carcinoma is a very difficult disease as you can see from the annual death rates in the United States; It's actually one of the top 10 diseases both in male as in female. What is even worse, is if we look at the 10 year mortality trend, you can see here that while the mortality trend is going downwards for a number of diseases, a number of different types of cancers, this is not the case for HCC. You can see both for men and for women, the mortality trend is actually going upwards in the past 10 years. Obviously, this tells us that there is a great need to come up with new treatment options for these type of patients; And what I'm trying to do now is, I'm trying to introduce you to the concept of immunotherapy, but before we go there and talk about immunotherapy for HCC, there is a few comments that I would like to make which explain to you the specifics that we have to consider when we talk about immunotherapy in the context of HCC.
The liver is a very special organ. HCC is the only tumor where we perform liver transplantation and the liver transplantation has quite a long history. It also shows us that the liver actually provides a very tolerogenic organ. Many years ago, before transplantation was performed, the first experiments were done in pigs that showed us that xenotransplantation is actually possible. Following up these very early studies in animal, there are studies in patients undergoing liver transplantation that show that you can actually wean the immunosuppression over time and patients will still remain with an intact organ. Now, another point that needs to be made here is the following, the liver is a very special organ because, it basically receives all the blood from the G.I. tract, with the portal vein. Now, in this blood there are a lot of microbial-associated molecular patterns. There's a lot of LPS, so the liver really is a filter for the body to clean out all this trash which is delivered from the G.I. tract.