Elucidation of immune suppression using tumor-infiltrating lymphocytes in perioperative immunotherapy for patients with hepatocellular carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17618
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Yamaguchi University
• Principal Investigator: Shindo Yoshitaro 山口大学, 医学部附属病院, 助教 (70749811)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肝細胞癌 / 免疫療法 / ワクチン療法

Outline of Final Research Achievements

Combination cancer vaccination with immune checkpoint inhibitors (ICIs) to restore T cell responses may be a potential therapeutic approach for hepatocellular carcinoma (HCC). We conducted therapeutic vaccine for the perioperative treatment of patients with resectable HCC. Our novel vaccination therapy has the potential to convert immunologically cold HCC tumors into hot tumors by inducing CD8+ T‐cell infiltration into tumors. Our results indicate that the upregulation of PD-1 and TIGIT expression on CD8+ T cells may restrict T cell responses in HCC patients. As such, it was suggested that the combination of ICIs may act synergistically to produce a high anti-tumor effect.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、がんワクチン療法は免疫原性の低いCold HCCが細胞傷害活性Ｔ細胞が浸潤するHotへ変化している可能性が示唆された。腫瘍浸潤細胞は免疫チェックポイント分子を高発現しているため、活性化が抑えられ十分な抗腫瘍効果を得られていない可能性がある。マウス腫瘍モデルを用いたワクチン療法と抗PD-1抗体の併用療法では、有意な抗腫瘍効果および生存期間延長効果を認めたことから、本ワクチン療法と抗PD-1抗体の併用は、相乗的に作用し高い抗腫瘍効果をもたらす可能性を示唆する学術的・社会的に意義ある成果を得た。