Development of a novel combination of tumor immunotherapy targeting the T-cell negative pathway and anti-tumor drugs

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09203
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Nara Medical University
• Principal Investigator: Hokuto Daisuke 奈良県立医科大学, 医学部, 助教 (70526821)
• Co-Investigator(Kenkyū-buntansha): 野見 武男 奈良県立医科大学, 医学部, 学内講師 (50570991)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 免疫療法 / 抗癌剤 / 肝細胞癌 / 大腸癌肝転移 / T細胞不活化経路

Outline of Final Research Achievements

Anticancer drugs are believed to have the potential to weaken the immune system. Combination therapy of immunotherapy and anticancer drugs has yet to be elucidated in many respects. In this study, we examined the combination therapy of immunotherapy and anticancer drugs for hepatocellular carcinoma and colorectal cancer liver metastases.
We found that the expression of HVEM, a target of immunotherapy, in resected specimens of colorectal cancer liver metastases and hepatocellular carcinoma was associated with poor prognosis. They also found that inhibition of VEM suppressed cancer cell proliferation. They also found that the addition of an anticancer drug suppressed cell proliferation even more. We attempted to develop a model to prove these findings in animal experiments. However, we were unable to establish an animal model during this study period. However, many of the findings obtained in the course of this research were submitted to an English journal for publication.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

近年、T細胞不活化経路をターゲットにした免疫療法が悪性腫瘍に対して臨床応用されている。一方、抗癌剤は一般的に免疫力を弱める可能性があるとされている。免疫療法と抗癌剤の併用療法は胃癌など一部の癌腫では臨床応用されつつあるものの、まだ解明されていない点も多い。もし免疫療法と抗癌剤が相乗的効果を持つのであれば多くの癌患者にとって有益な情報となる。本研究では、肝細胞癌と大腸癌肝転移に対して免疫療法と抗癌剤の併用療法が一部実験において有効な結果を示した。これは免疫療法と抗癌剤の併用が抗腫瘍効果を増強する可能性を示した考えられる。