Proliferating immune cells
Hepatocellular carcinoma (HCC) is a common type of liver cancer triggered primarily by secondary causes, such as hepatitis infections or alcohol-induced cirrhosis. The medical condition causes 662,000 deaths worldwide per year, and is particularly prevalent in Southeast Asia and Africa. Treatment options for HCC remain limited for people with advanced disease and existing clinical methods for forecasting survival among newly diagnosed patients remain poor, so researchers have been on the lookout for early biomarkers to better predict long-term survival.
To that end, Jean-Pierre Abastado at the A*STAR’s Singapore Immunology Network and co-workers began probing the tumor immune microenvironment for clues. By characterizing the immune system in liver tumors, they have discovered a molecular signature that can predict patients’ chance of survival early in the development of the disease — a finding that should open the door to new anti-cancer treatments.
“The understanding of the immune mechanisms leading to prolonged patient survival could be used to develop novel therapeutic strategies,” says Abastado.
Two years ago, Abastado and his team showed that patients with higher expression of innate immune genes in their tumors also tended to live longer. The researchers have now expanded those findings into a predictive test. Using a group of Singaporean patients with HCC, they measured the expression levels of 14 immune genes — including those that express chemokines, inflammatory cytokines and leukocyte markers — and derived a prognostic signature of survival. To validate the assay, they turned to independent cohorts from Hong Kong and Switzerland, and showed that the test worked with a high degree of accuracy irrespective of patients’ ethnic origins or the original cause of their liver cancer.
Importantly, the test predicted the survival of people with early- but not late-stage disease, suggesting that the protective immune microenvironment has to be established early to have a positive impact on disease progression. “If the disease is too advanced,” says Abastado, “the immune milieu has little impact.”
In addition to hinting at new immunotherapies to treat liver cancer, the findings should help doctors manage the cancer better. By flagging those patients with a favorable immune profile, the test could now be used to identify individuals best suited to receive liver transplants or other interventions. “The ability to predict patient survival may be useful in identifying HCC patients more likely to benefit from aggressive treatments,” says Abastado. He hopes that his work could help save millions of lives every year.
The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network.
