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Precision Cancer Immunotherapy Target for HPV-positive Oropharyngeal Cancer Discovered

Joint research team from the College of Life Science and Biotechnology and Medical Center 

discovers precision cancer immunotherapy target for human papillomavirus (HPV)-positive oropharyngeal cancer

Single-cell precision genome analyses were performed

A novel mechanism for determining the effectiveness of immunotherapy for HPV-positive oropharyngeal cancer was presented

The study findings demonstrated possibilities for developing precision immunotherapy for patients with oropharyngeal cancer


A joint research team from the College of Life Science and Biotechnology and Medical Center revealed major cellular and molecular factors that affect the response to immunotherapy via single-cell precision genome analyses of cancer and immune cells in the tumor microenvironment of patients with oropharyngeal cancer. The findings were published on June 11 in the ‘Journal for ImmunoTherapy of Cancer’ (IF: 10.9), a prestigious journal in anticancer immunotherapy.


Oropharyngeal cancer is known to have poor prognosis, and tobacco and alcohol consumption have been identified as its major causes. Recently, there has been a steady increase in oropharyngeal cancer caused by human papillomavirus (HPV) infection. HPV-positive patients with oropharyngeal cancer demonstrated relatively better prognosis than HPV-negative patients under general anticancer therapy. However, a recent large-scale clinical trial has confirmed that there is no significant difference between the prognosis of HPV-positive and -negative patients in response to cancer immunotherapy. Understanding the cause of such results remained an urgent task.

To address this problem, the research team compared and analyzed HPV-positive and -negative oropharyngeal cancer tissues at the single-cell level. They discovered that the expression of specific CD161 receptors in cytotoxic T-cells of HPV-positive patients with oropharyngeal cancer counteracts the effect of anticancer immunotherapy. The expression of CD161 receptors inhibits the expression of CD161 ligands in B cells, thereby preventing the formation of tertiary lymphatic structures that are crucial in immune-mediated anticancer mechanisms. This explains why HPV-positive patients with oropharyngeal cancer have a better prognosis than HPV-negative patients in response to general anticancer treatments, but not in response to immunotherapy.


The results of this study confirmed that the expression of specific CD161 receptors on cytotoxic T-cells can be used to predict the effect of cancer immunotherapy in HPV-positive oropharyngeal cancer. Furthermore, future development of technology targeting CD161 receptors is expected to dramatically improve the efficacy of anticancer immunotherapy in HPV-positive patients with oropharyngeal cancer.


Professor Insuk Lee, the corresponding author, explained the significance of this research: “This research provides an important foundation for future development of therapeutic technology by presenting a novel method that can predict the response of patients with oropharyngeal cancer toward immunotherapy and improve its therapeutic effects.”


Professor Yoon Woo Koh remarked, “The results confirmed that the expression of specific CD161 receptors on cytotoxic T-cells can be used to predict the efficacy of immunotherapy against HPV-positive oropharyngeal cancer.” He added, “the development of CD161 receptor-inhibiting technology in the future will dramatically enhance the efficacy of immunotherapy for HPV-positive patients with oropharyngeal cancer.”


This study was led by Professor Insuk Lee and Professor Sang-Jun Ha from the College of Life Science and Biotechnology, Professor Yoon Woo Koh from the Department of Otorhinolaryngology, Professor Hye Ryun Kim from the Division of Medical Oncology, and was supported by the National Research Foundation of Korea Biomedical Technology Development Next-Generation Applied Omics Project and Leading Research Center Support Project. The first authors of the paper are Junha Cha, PhD candidate from the Department of Biotechnology, Professor Da Hee Kim, and researcher Gamin Kim from the Medical Center.


Find out more: 

Title of article: Single-cell analysis reveals cellular and molecular factors counteracting HPV-positive oropharyngeal cancer immunotherapy outcomes

DOI: https://jitc.bmj.com/content/12/6/e008667

Journal: Journal for ImmunoTherapy of Cancer

Contact corresponding author: Prof. Insuk Lee (insuklee@yonsei.ac.kr)

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