HPV-related head and neck cancer: immunological analysis and cancer immunotherapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03834
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Gunma University
• Principal Investigator: CHIKAMATSU KAZUAKI 群馬大学, 大学院医学系研究科, 教授 (30301378)
• Co-Investigator(Kenkyū-buntansha): 松山 敏之 群馬大学, 医学部附属病院, 講師 (10815137)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 頭頸部癌 / ヒト乳頭腫ウイルス / がん免疫

Outline of Final Research Achievements

We investigated the immunological differences between HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) using public database and clinical samples.
HPV-positive HNSCC exhibited higher infiltration of various immune cells and higher expression of cytotoxic-related molecules, suggesting that antitumor immune responses were activated in HPV-positive HNSCC compared to HPV-negative HNSCC. We next evaluated the presence of tumor antigen-specific T cell responses in HPV-positive HNSCC. Blockade of checkpoint pathways could enhance tumor antigen-specific T-cell responses in certain patients, probably via exhausted CD4+T cells. Finally, we examined the relationship between EMT-related gene expression in circulating tumor cells (CTC) and the activation status of peripheral blood T cells. We revealed that SNAI1-high CTCs reflect the antitumor activity of circulating T cells in patients with HPV-positive HNSCC.

Free Research Field

耳鼻咽喉科

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害剤の登場は、がん治療においてパラダイムシフトをもたらした。同時に様々ながん種において抗腫瘍免疫応答機構についての解明が急速に進んでいる。本研究においてHPV陽性頭頸部癌とHPV陰性頭頸部癌の免疫病態の違いを様々な観点から比較解析することで、HPV陽性頭頸部癌のがん微小環境と末梢血における免疫病態の解明だけでなく、免疫療法の新しい標的分子や免疫学的バイオマーカーの同定につながる有用な知見を得られた。