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Researchers identify immune biomarker of response in patients with advanced liver cancer

Roswell Park Comprehensive Cancer Center immunology researchers have uncovered a biomarker that may help explain why some patients respond better than others to a common chemotherapy treatment for liver cancer.

They hope that their analysis of immune responses among patients receiving sorafenib can lead to more individualised treatment options and better overall outcomes for patients diagnosed with the disease.

The 4-year study, led by Department of Immunology scientist Yasmin Thanavala, PhD, has been published in the journal JCI Insight.

Hepatocellular carcinoma (HCC), which can arise from liver cirrhosis, is the most common form of liver cancer.

The mainstay oral chemotherapy treatment for patients with advanced HCC is sorafenib — but side effects from this drug may cause many patients to miss doses or discontinue treatment.

The researchers, who included Renuka Iyer, MD, Section Chief for Gastrointestinal Oncology at Roswell Park, collected blood samples from 30 patients both before treatment and at two timepoints during treatment with sorafenib.

They observed elevated levels of a subset of CD8 cytotoxic T-cells (CD8 Ki67 T cells producing IFNg) producing interferon type II, an important immune protein that destroys tumour cells and significantly reduces risk of death over time.

Similarly, CD8 cells showed an increase in granzyme B, an important enzyme that helps drive cell death.

Additional findings showed that patients with a high ratio of CD4 T-effector/T-regulatory cells prior to treatment showed significant improvement in both progression-free and overall survival.

Decreased numbers of two important immune checkpoint proteins expressed on T-cells — PD-1 and CTLA-1 — suggests that a combination treatment of sorafenib with checkpoint inhibitors such as nivolumab and pembrolizumab could produce positive results in the future.

“Studying biomarkers that correlate with progression-free or overall survival can help reduce exposure to therapies that have an impact on a patient’s quality of life and survival,” said Dr Thanavala, who led this research. “Utilising this information, our evidence supports the rationale that patients could benefit from a regimen of sorafenib and immunotherapy, which could help with anti-tumour immunity and improve the magnitude and strength of anti-tumour responses.”

Source: Roswell Park



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