Establishment of combined cancer immunotherapy using neoantigen-induced mouse model

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16771
• 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: Shimane University
• Principal Investigator: Ishibashi Tomoka 島根大学, 学術研究院医学・看護学系, 助教 (40643648)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 癌免疫

Outline of Final Research Achievements

We reported that PD-1/PD-L1 inhibitors might be effective in patients with MSI-high endometrial cancers, and that MSI-high will be a potential biomarker for PD-1/PD-L1 inhibitors. In addition, we also reported that MSI-high is frequently observed in dedifferentiated endometrial cancers, and in undifferentiated cancer portions, the effect of immune checkpoint inhibitors can be expected. We speculated that combined treatment with anti-cancer drug and immune check point inhibitors may be effective for dedifferentiated endometrial cancers. Furthermore, we concluded that immune checkpoint inhibitors may be effective in patients with cervical adenocarcinoma with high PD-L1 expression. On the other hand, according to our genetic analysis in ovarian cancers, the frequency of MSI-high is estimated to be about 5%. Therefore, combined immune cancer treatment in combination with other anti-cancer drugs should be needed for patients with ovarian cancers.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

卵巣癌では既に免疫チェックポイント阻害薬の奏功が報告されたが、治療効果が特に期待される集団については検討されていなかった。MSIまたはPOLE変異が関連する癌はmutation burden richと考えられるが、当科の研究では卵巣癌におけるMSI-highの頻度は5％程度であった。卵巣癌に対する免疫チェックポイント阻害薬の効果が期待されたが、他の薬剤と併用する複合的がん療法の必要性が示唆された。卵巣癌におけるこれらmutation burden richな腫瘍と免疫チェックポイント阻害薬の効果を検討することは、今後個別化した治療を選択する上で重要であり、今後臨床応用の可能性がある。