Roswell Park Researchers Identify Immune Biomarker of Response in Patients With Advanced Liver Cancer
Findings may guide decisions about which patients will benefit most from treatment with sorafenib
Advanced hepatocellular carcinoma (HCC) is commonly treated with sorafenib
Subset of CD8+ cells are biomarker linked with survival benefit, team shows
Evidence could lead to more individualized treatments for liver cancer patients
BUFFALO, N.Y. — 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 individualized treatment options and better overall outcomes for patients diagnosed with the disease.
Dr. Yasmin Thanavala and team found that elevated levels of a subset of cytotoxic CD8+ T cells were a good biomarker of survival for patients taking sorafenib for liver cancer.
The 4-year study, led by Department of Immunology scientist Yasmin Thanavala, PhD, was published online this week in JCI Insight, a peer-reviewed journal published by the American Society for Clinical Investigation, and also to be highlighted in the journal’s JCI This Month digest for September 2019.
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 IFN?? producing interferon type II, an important immune protein that destroys tumor 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,” says Dr. Thanavala, who led this research. “Utilizing this information, our evidence supports the rationale that patients could benefit from a regimen of sorafenib and immunotherapy, which could help with antitumor immunity and improve the magnitude and strength of antitumor responses.”
The study, “Augmentation of IFN-y+ CD8+ T cell responses correlates with survival of HCC patients on sorafenib therapy,” is available at insight.jci.org. This work was supported by the National Cancer Institute, or NCI (grant P30CA016056), the National Comprehensive Cancer Network® (NCCN®) Oncology Research Program from general research support provided by Bayer U.S LLC (NCCNSORA0002), and by donations to Roswell Park.
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Roswell Park Researchers Identify Immune Biomarker of Res...