Samsung Seoul Hospital Research Team Identifies 'Genomic Characteristics' Optimizing Immunotherapy for Liver Cancer

Possibility of Immunotherapy for Intractable Liver Cancer Revealed
Based on Ultra-Precision Genome Analysis

Professors Baek Yong-han and Lim Ho-young, Samsung Medical Center. [Photo by Samsung Medical Center]

[Asia Economy Reporter Lee Gwan-joo] A new path has opened to enhance the effectiveness of immuno-oncology treatment for hepatocellular carcinoma, which is difficult to treat.

Professor Baek Yong-han from the Department of Gastroenterology at Samsung Medical Center, along with Professors Lim Ho-young and Hong Jung-yong from the Department of Hematology and Oncology, announced on the 8th that they have identified genomic characteristics influencing the responsiveness of liver cancer patients to immune checkpoint inhibitors.

Hepatocellular carcinoma accounts for the majority of primary malignant liver cancers. It is the fourth leading cause of cancer-related deaths worldwide and is known to have a particularly high incidence in Asia. Pembrolizumab, an immuno-oncology drug, has been approved as a second-line treatment for hepatocellular carcinoma; however, identifying predictive and reliable biomarkers to forecast treatment response remains a challenge in clinical practice.

Accordingly, the research team conducted an integrated genomic analysis study on 60 hepatocellular carcinoma patients treated with pembrolizumab to facilitate the identification of predictive markers that can distinguish responders from non-responders.

According to the research team, among the 60 hepatocellular carcinoma patients who received immuno-oncology treatment, 6 patients responded to the treatment, resulting in an overall response rate of 10%. Clinical pathological analysis identified female sex, presence of the PD-L1 gene targeted by immunotherapy, and a low neutrophil-to-lymphocyte ratio (NLR) as factors associated with a positive response to immunotherapy.

Conversely, in the non-responder group, somatic mutations in the CTNNB1 gene and amplification of the MET gene were observed, showing distinct differences. Furthermore, RNA sequencing analysis revealed that increased levels of T cell cytotoxicity through activation of T cell receptor (TCR) signaling were factors inducing a response to immunotherapy.

Additionally, single-cell sequencing analysis of 10 peripheral blood mononuclear cell (PBMC) samples before and after treatment showed that patients with partial or stable responses to immuno-oncology treatment exhibited an increase in cytotoxic CD8+ T cells, whereas non-responders showed increased activation of CD14+ and CD16+ monocytes and neutrophil-related pathways.

Based on these findings, the research team evaluated that conditions optimized for immuno-oncology treatment include tumors rich in tumor-infiltrating cytotoxic T cells, increased activated circulating CD8+ T cells, and fewer neutrophil-related markers.

Lead researcher Professor Baek Yong-han explained, “This study shows that not only the characteristics of the tumor tissue itself in each cancer patient but also the nature and distribution of the patient’s immune cells and T cells are very important for the response to immunotherapy.” Park Jun-oh, director of the Precision Medicine Innovation Research Center at Samsung Medical Center (Professor of Hematology and Oncology), expressed hope, saying, “These research results will help discover next-generation immunotherapy methods for cancer patients who are unresponsive to existing immunotherapies.”

This study was conducted as a joint research project between the Precision Medicine Innovation Research Center and the Department of Gastroenterology at Samsung Medical Center, supported by the Ministry of Health and Welfare’s Research-Centered Hospital Development R&D Project, and was recently published in the internationally renowned journal ‘Genome Medicine (IF 11.117).’

This content was produced with the assistance of AI translation services.