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Can Liver Cancer Immunotherapy Efficacy Be Improved Through Novel Approaches?

IMMUNOTHERAPY uses humanised antibodies, namely immune checkpoint inhibitor (ICIs), to block cellular pathways that inhibit immune system cells, allowing these cells to protect the body and help fight cancer. Despite the highly promising initial excitement surrounding immunotherapy, most people with cancer respond poorly, or not at all, to treatments using ICIs. This is especially true in patients with liver cancer. 

Recent research carried out at the University of California San Diego, California, USA, has sought to increase the efficacy of immunotherapy in patients with liver cancer by treatment in combination with adjuvant therapies. Gen-Sheng Feng, lead study author and Professor of Pathology, School of Medicine, Division of Biological Sciences, University of California San Diego, demonstrated that liver cancer can be rendered highly responsive to the ICI anti-PD-L1 by treatment in combination with a synthetic double-stranded RNA molecule named polyIC. 

Examining tumour models in mice, researchers found combination of the two reagents, polyIC and anti-PD-L1, showed remarkable synergistic effects in liver tumour inhibition. Results were not found when either reagent was used as a monotherapy. Analysis suggested that efficacy of combined treatment largely arose due to boosting of cytotoxic CD8 T cells and innate immune cells by polyIC, alongside the blocking of inhibitory T lymphocyte pathways with anti-PD-L1 antibody.  

A successful immunotherapy must rely on overcoming hepatic immune-tolerance and disrupting the immune evasion mechanism in the tumour microenvironment,” stated Feng. “The reason we are excited is that the data suggest a possibility that liver cancer can be turned highly responsive to immunotherapy…There is a promising future that liver cancer patients can benefit from immunotherapy.”