How chronic inflammation tips the balance of immune cells to promote liver cancer

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Study explains success of some types of cancer immunotherapy, provides new targets for the development of additional immunotherapies

Chronic inflammation is known to drive many cancers, especially liver cancer. Researchers have long thought that’s because inflammation directly affects cancer cells, stimulating their division and protecting them from cell death. But University of California San Diego School of Medicine researchers have now found that chronic liver inflammation also promotes cancer by suppressing immunosurveillance — a natural defense mechanism in which it’s thought the immune system suppresses cancer development.

The study is published November 8 in Nature.

“Recent successes in cancer immunotherapy — in the form of immune checkpoint inhibitors and adoptive T cell transfer — demonstrate how activated immune cells can eradicate tumors, but until now we didn’t fully appreciate immunosurveillance or the role of adaptive immunity in tumor formation,” said senior author Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology at UC San Diego School of Medicine. “This study provides one of the strongest and most direct demonstrations that adaptive immunity actively prevents liver cancer.” Karin led the study with first author Shabnam Shalapour, PhD, an assistant professor in his group.

The team used a new mouse model of liver cancer in this study. Rather than artificially triggering cancer by engineering genetic mutations, this model more closely mimics human liver cancer in that tumors develop as a natural consequence of non-alcoholic steatohepatitis (NASH), a chronic metabolic disorder that causes liver damage, fibrosis and numerous cell mutations. NASH is associated with obesity and is expected to soon become the leading cause of liver cancer in the U.S. and other Western countries, Karin said.