NEW YORK, March 24, 2021 /PRNewswire-PRWeb/ --
Immunotherapy is not only significantly less effective in liver
cancer patients who previously had a liver disease called
non-alcoholic steatohepatitis (NASH), but actually appears to fuel
tumor growth, according to a Mount
Sinai study published in Nature in March. NASH affects as
many as 40 million people worldwide and is associated with obesity
and diabetes.
The researchers led a large international collaboration to
investigate immunotherapy's effect on hepatocellular carcinoma
(HCC), a deadly liver cancer, caused by NASH. They conducted a
meta-analysis of three randomized phase 3 human trials that tested
immunotherapy in HCC and found that in non-viral HCC cases, such as
NASH-related HCC, therapy was significantly less effective than in
viral-related cases.
In addition, this study found in animal models that
immunotherapy with anti-PD1 inhibitors actually led to tumor growth
instead of the intended effect of aiding the immune system to kill
cancer cells and shrink the tumor. In these models, researchers
identified immune cells called CD8+PD1+ as drivers of these
phenomena. These cells were found to be dysfunctional and incapable
of immunosurveillance.
"In addition to allowing clinicians to optimize treatment
protocols based on the underlying liver disease, the knowledge
obtained through this study will provide a backbone for the design
of further combination treatments to overcome current limitations
and improve survival for patients with these underlying liver
conditions," said senior and co-corresponding author Josep Llovet, MD, PhD, Founder and Director of
the Liver Cancer Program at The Tisch Cancer Institute and
Professor of Medicine (Liver Diseases) at the Icahn School of
Medicine at Mount Sinai. "These
results also highlight the need for refined therapeutic strategies
aimed at treating both the tumor as well as the microenvironment
associated with distinct underlying liver disease."
Non-alcoholic fatty liver disease (NAFLD), a condition that is a
precursor of NASH, is estimated to affect 25 percent of the
population worldwide, and up to 20 percent of these patients will
progress to having NASH. NASH is an emerging risk factor for HCC,
which led to this study's investigation of immunotherapy's effects
on NASH-related HCC. While immunotherapy has clinical benefit for
hepatocellular carcinoma, this study's findings are important
because a quarter of all HCC patients have NASH.
The meta-analysis in this study was conducted on three
high-quality phase 3 trials that included more than 1,600 HCC
patients treated with anti-PD1 immunotherapy. This study represents
a major international collaborative effort from 110 investigators
from 81 institutions.
Amaia Lujambio, PhD; Thomas Marron, MD, PhD; and Philipp Haber, MD, from Mount Sinai contributed significantly to this
study and are also co-authors.
About the Mount Sinai Health System
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York City's largest academic medical system, encompassing
eight hospitals, a leading medical school, and a vast network of
ambulatory practices throughout the greater New York region. Mount Sinai is a national and international
source of unrivaled education, translational research and
discovery, and collaborative clinical leadership ensuring that we
deliver the highest quality careāfrom prevention to treatment of
the most serious and complex human diseases. The Health System
includes more than 7,200 physicians and features a robust and
continually expanding network of multispecialty services, including
more than 400 ambulatory practice locations throughout the five
boroughs of New York City,
Westchester, and Long Island. The Mount Sinai Hospital is
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Top 20 Best Hospitals in the country and the Icahn School of
Medicine as one of the Top 20 Best Medical Schools in country.
Mount Sinai Health System hospitals are consistently ranked
regionally by specialty and our physicians in the top 1% of all
physicians nationally by U.S. News & World Report.
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Media Contact
Marlene Naanes, Mount Sinai
Health System, 212-241-9200, marlene.naanes@mountsinai.org
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SOURCE Mount Sinai Health System