The quest for immune checkpoint inhibitor biomarker derived from tumor exsosomes

Research Project

Project/Area Number	16K15543
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Dermatology
Research Institution	Chiba University
Principal Investigator	Matsue Hiroyuki 千葉大学, 大学院医学研究院, 教授 (10250424)
Research Collaborator	MATSUOKA yuumi SUEHIRO keisuke YAMAMOTO yosuke
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000) Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	悪性黒色腫 / メラノーマ / バイオマーカー / エクソソーム / RT-LAMP法 / 皮膚腫瘍学
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.
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。