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CD8-Positive, Ki67-Positive T Cells Producing Interferon Gamma as a Biomarker of Response to Sorafenib Therapy in Patients With Advanced HCC

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Key Points

  • Researchers observed elevated levels of a subset of CD8-positive cytotoxic T cells (CD8-positive, Ki67-positive T cells producing interferon gamma) producing interferon type II.
  • Patients with a high ratio of CD4-positive T-effector/T-regulatory cells prior to treatment showed significant improvement in both progression-free and overall survival.

Immunology researchers have uncovered a biomarker that may help explain why some patients respond better than others to sorafenib, a common chemotherapy used in the treatment of hepatocellular carcinoma (HCC). Their analysis of immune responses among patients receiving sorafenib, published by Kalathil et al in JCI Insight, may lead to more individualized treatment options and better overall outcomes for patients diagnosed with the disease.

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

Methods and Findings

Researchers 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-positive cytotoxic T cells (CD8-positive, Ki67-positive T cells producing interferon gamma) producing interferon type II, an important immune protein that destroys tumor cells and significantly reduces risk of death over time. Similarly, CD8-positive 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-positive 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—programmed cell death protein 1 and cytotoxic T-lymphocyte–associated antigen 4—suggested that a combination treatment of sorafenib with checkpoint inhibitors such as nivolumab and pembrolizumab could produce positive results in the future.

The authors concluded, “A high baseline CD4-positive T-effector/T-regulatory [cell] ratio is a potential biomarker of prognostic significance in hepatocellular carcinoma. CD8-positive, Ki67-positive T cells producing interferon gamma are a key biomarker of response to sorafenib therapy resulting in survival benefit.”

“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 lead study Yasmin Thanavala, PhD, a scientist in the Department of Immunology at Roswell Park Comprehensive Cancer Center. “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.”

Disclosure: For full disclosures of the study authors, visit insight.jci.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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