Cookies

Like most websites The Pathologist uses cookies. In order to deliver a personalized, responsive service and to improve the site, we remember and store information about how you use it. Learn more.
Subscribe to Newsletter
Subspecialties Biochemistry and molecular biology, Oncology

A Longer Life With Liver Cancer

Statistics for patients diagnosed with liver cancer are bleak – only 18.4 percent survive past five years in the US (1). The most common form of primary liver cancer, hepatocellular carcinoma (HCC), is notoriously difficult to treat, with multikinase inhibitors, such as sorafenib and regorafenib, extending overall survival by less than three months. But the future looks brighter; new research from a team led by Mien-Chie Hung at the University of Texas MD Anderson Cancer Center shows that a cellular pathway closely linked to cancer may prolong immunotherapy and reduce its side effects.

The pathway in question forms when the interleukin-6 (IL-6) protein activates the Janus kinase 1 (JAK1) enzyme. This process often occurs in tumors and has been linked to the regulation of programmed death ligand 1 (PD-L1), a protein known to suppress the immune system. “We discovered that the IL-6/JAK1 pathway enhances PD-L1 expression in HCC cells, making it a promising target for the development of treatments,” Hung explains.

To combat the action of the IL-6/JAK1 pathway, the team found that combining anti-IL-6 antibodies and anti-T-cell immunoglobin mucin-3 (anti-Tim-3) boosted T cell-killing effects in mouse models (2). They also showed that, across 183 HCC patients, those with high IL-6 expression had elevated PD-L1 expression – confirming the link between high IL-6 levels and poor prognosis.

On the potential applications of their discovery, Hung says, “Anti-IL-6 antibodies could be used to prevent PD-L1 glycosylation, leading to PD-L1 downregulation as well as impeding its localization on the cell surface.” Given that immune checkpoint inhibitors have been shown to stimulate IL-6 production, blocking the IL-6 pathway could also lessen the side effects of immunotherapy and extend its duration for HCC patients.

After showing synergistic efficacy in animal models, a combined therapy of anti-IL-6 and anti-Tim-3 certainly appears promising. “We are looking forward to collaborating with the scientific and medical community to initiate clinical trials to treat HCC patients, who currently lack access to effective treatment,” says Hung.

Receive content, products, events as well as relevant industry updates from The Pathologist and its sponsors.
Stay up to date with our other newsletters and sponsors information, tailored specifically to the fields you are interested in

When you click “Subscribe” we will email you a link, which you must click to verify the email address above and activate your subscription. If you do not receive this email, please contact us at [email protected].
If you wish to unsubscribe, you can update your preferences at any point.

  1. National Cancer Institute, “Cancer stat facts: liver and intrahepatic bile duct cancer” 2016. Available at: bit.ly/2j97Dnm. Accessed August 13, 2019.
  2. LC Chan et al., “IL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to promote cancer immune evasion”, J Clin Invest, 129, 3324–3338 (2019). PMID: 31305264.
About the Author
Luke Turner

While completing my undergraduate degree in Biology, I soon discovered that my passion and strength was for writing about science rather than working in the lab. My master’s degree in Science Communication allowed me to develop my science writing skills and I was lucky enough to come to Texere Publishing straight from University. Here I am given the opportunity to write about cutting edge research and engage with leading scientists, while also being part of a fantastic team!

Most Popular
Register to The Pathologist

Register to access our FREE online portfolio, request the magazine in print and manage your preferences.

You will benefit from:
  • Unlimited access to ALL articles
  • News, interviews & opinions from leading industry experts
  • Receive print (and PDF) copies of The Pathologist magazine

Register