2018 Fiscal Year Final Research Report
The quest for immune checkpoint inhibitor biomarker derived from tumor exsosomes
| Project/Area Number |
16K15543
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | Chiba University |
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Principal Investigator |
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| Research Collaborator |
MATSUOKA yuumi
SUEHIRO keisuke
YAMAMOTO yosuke
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 悪性黒色腫 / メラノーマ / バイオマーカー / エクソソーム |
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| Outline of Final Research Achievements |
At the beginning of the study, we focused on PD-L1 in exosomes in the plasma of malignant melanoma patients and sought to find appropriate biomarkers to select cases that could be expected to be effective before administration of the immune checkpoint inhibitor. At that time, in 2018, PD-L1 in exosomes was reported to be associated with immunosuppression and anti-PD-1-response. But, PD-L1 are also elevated in inflammation, and are expected to have low specificity. Also, in recent years, positive correlations between tumor-specific mutant antigens (neoantigens) and the effects of immune checkpoint inhibitors have been reported, and identification of neoantigens was considered to be important for the effect prediction. Therefore, we have extracted DNA from melanoma lesions and comprehensively analyzed cancer-related genes using gene panel analysis to search for neoantigens.
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| Free Research Field |
皮膚免疫
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| Academic Significance and Societal Importance of the Research Achievements |
免疫チェックポイント阻害薬は悪性黒色腫以外の癌にも適応が拡大されて使用されているが、この種の薬剤の共通の問題点は、担がん患者さんの抗腫瘍免疫の状態を適切に評価する方法がなく、抑制されている抗腫瘍免疫能も評価できないことである。この種の薬剤の効果は、抑制を解除したときの抗腫瘍免疫の強さが関与しており、投与前に効果が期待できる症例の適切なバイオマーカーを見つけることは、適応患者を選択し、医療費削減にも寄与する。我々の研究の継続は、日本人の悪性黒色腫患者さんのneoantigenを同定し、それに対する特異的抗腫瘍免疫を評価する第一歩として重要である。
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