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Printable Handouts
Navigable Slide Index
- Introduction
- HCC: annual deaths and mortality trend
- Liver induced tolerance
- Distribution of cell types in the liver
- Immunotherapy and HCC?
- HCC: an inflammation associated cancer?
- Immune correlatives correlate with outcome in HCC
- Immunotherapy’s potential
- Age-standardised prevalence of obesity in men
- Age-standardised prevalence of obesity in children
- Non-alcoholic steatohepatitis (NASH) - HCC
- MYC transgenic HCC mouse model
- MCD-induced non-alcoholic steatohepatitis
- NASH promotes hepatocarcinogenesis
- Selective CD4+ T cell loss in mice with NASH
- Selective CD4+ T cell loss exclusive to liver
- Selective CD4+ T cell loss in other NAFLD models
- Intrahepatic CD4+ T cells die in NASH/myc mice
- Linoleic acid causes selective CD4+ T cell loss
- Mouse diet composition
- Linoleic acid enriched diet causes CD4+ T cell loss
- C18:2 increases mitochondrial ROS production
- NAC treatment prevents CD4+ T cell loss
- CD4+ T cells, C18:2 and NASH in patients
- Mechanism of increased ROS production
- Summary: model of HCC
- Hallmarks of senescent cells
- Hepatocyte-specific senescence in cirrhosis
- Senescence induction
- SASP-induced immune cells in the liver
- Effects of myeloid cells on tumor growth
- NK cells can prevent tumor growth
- SASP-induced immune cells in the liver (model)
- Peritumoral senescence & poor survival
- Peritumoral senescence & myeloid cells
- Correlation of p16/p21 and CCR2
- Analysis of CD14+ cells in peripheral blood
- CD14+ HLA-DR(low) cells in peripheral blood
- MDSC inhibit T cell function in vitro
- MDSC inhibit NK cell function
- EASL–EORTC clinical practice guidelines: HCC
- Rationale to use immunotherapy in HCC
- Immunotherapy trials in HCC
- Immune approaches tested in HCC
- Immunological effects of ablative therapies
- RFA correlates with better survival
- TACE associated with better clinical outcome
- Induction by ablative therapy
- A pilot study of Tremelimumab
- Pilot study: Inclusion criteria
- Patient characteristics
- Adverse events
- Case: Effects of ablation
- Efficacy (1)
- Efficacy (2)
- Viral immunity
- Tumor biopsies
- Tumor-specific T cell responses
- Summary: Ablation and anti-CTLA4
- Immune checkpoint inhibitors in HCC
- Ongoing immunotherapy trials in HCC
- Glypican 3
- Ongoing clinical trials
- Future immunotherapy trials
Topics Covered
- Hepatocellular carcinoma (HCC) background and overview
- Non-alcoholic steatohepatitis (NASH) and HCC
- Immune suppressor mechanisms in tumour environments
- Ongoing and future immunotherapy trials in HCC
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Greten, T. (2017, July 31). Immunotherapy of hepatocellular carcinoma [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/OXQL1823.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Tim Greten has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: Immunotherapy of Cancer
Transcript
Please wait while the transcript is being prepared...
0:00
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.
0:14
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.
1:19
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.