Development of novel immunotherapy by identification and proliferation of cervical cancer-specific stem cell memory T cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16813
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Nihon University (2020); Keio University (2018-2019)
• Principal Investigator: KATOH Yuki 日本大学, 医学部, 助教 (60733649)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ステムセルメモリーT細胞 / 免疫チェックポイント阻害薬 / 抗PD-1抗体療法

Outline of Final Research Achievements

Stem cell memory T (Tscm) cells are a novel subset of memory T cells. Compared with other memory T cells (e.g., central memory/ effector memory T cell), Tscm cells are less sensitive, long-lived, and proliferate quickly in response to antigenic stimulation to produce large numbers of effector T cells, which is expected to be applied to cancer immunotherapy. We investigated the mechanism of tumor antigen-specific CD8+ Tscm cells proliferation and the differentiation into effector T cells. Furthermore, we evaluated several candidates that might promote the proliferation of antigen-specific CD8+ Tscm cells, and found that these drugs enhanced the therapeutic effect of anti-PD-1 antibody in a tumor-bearing mouse model.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

Tscm細胞の発生・増殖・分化のメカニズムは未だ不明な点が多いことから、本研究により得られた知見は、その理解に役立つものと考えている。さらに、抗PD-1抗体などの免疫チェックポイント阻害薬単独での奏効率は、効果を示すがん種においても20%程度であり、不応例に対する併用療法の開発が重要な課題となっているが、我々の同定した標的分子の阻害剤を併用することにより、より効果的な複合がん免疫療法の提供が可能となる。