2022 Fiscal Year Final Research Report
Development of biomarkers for predicting the effectiveness of immune checkpoint inhibitors - potential of autoantibodies in the bloodstream
| Project/Area Number |
20K17050
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Okayama University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 膵癌 / 抗PD-1抗体 / バイオマーカー |
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| Outline of Final Research Achievements |
We discovered that there is a certain number of pancreatic cancer patients who test positive for antibodies of PD-1 molecule, and investigated whether this could serve as a biomarker for predicting the effectiveness of chemotherapy. We measured the anti-PD-1 antibody levels in the serum of pancreatic cancer patients undergoing chemotherapy using an indirect ELISA method.The patients with high anti-PD-1 antibody group had a significantly longer survival compared to the patients with low-antibody group, and we found that the disease control rate (DCR) was significantly higher in the high antibody group. We investigated the correlation between PD-L1 staining in the tumor site and anti-PD-1 antibody using reseced samples, however any significant correlation were found. We guess that antibody production may depend on the individual. We hypothesize that PD-1 antibody-positive patients inhibit PD-1-PD-L1 binding and contribute to cellular immune activity.
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| Free Research Field |
消化器病
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| Academic Significance and Societal Importance of the Research Achievements |
近年、多くの癌種での有用性が報告されているチェックポイント阻害剤であるが、膵癌に対しては効果が乏しいとされている。今回の検討で血清中にPD-1に対する自己抗体があることが判明し、抗体価が高い群では、生命予後が良好で、抗腫瘍効果が良好な結果であった。抗PD-1抗体価が高い状態では、PD-1ーPD-L1の結合を阻害することで細胞免疫が活性化していると考えられる。逆に抗体価が低い症例では、既存のPD-1抗体の使用により抗腫瘍効果を示すことも期待される。細胞性免疫の活性化には、膵癌特有の線維化なども関与しており、一元的には論述できないが、腫瘍側因子も整理していく事で、次世代の治療に繋がる可能性がある。
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