がん研セミナー（6月10日）のお知らせ

演題：Genetic mechanism involving PD-1 ligands to promote immune evasion in multiple cancers

演者：片岡　圭亮　博士（国立がん研究センター  研究所　分子診断・個別化医療開発グループ　分子腫瘍学分野  分野長）

抄録：Successful treatment using anti-PD-1/PD-L1 antibodies has highlighted a critical role of immune evasion in cancers. Here we demonstrate a novel genetic mechanism of immune evasion caused by structural variations (SVs) disrupting the 3′-UTR of PD-L1 in various malignancies. Initially, using whole-genome sequencing of adult T-cell leukemia (ATL), followed by pan-cancer analysis of >10,000 cases in 33 cancer types, we identified PD-L1 SVs in ATL, B-cell lymphoma, and several solid cancers. All SVs affected the 3′-UTR and were associated with a marked increase of PD-L1 expression. CRISPR-mediated disruption of the 3′-UTR induced PD-L1 overexpression and promoted tumor growth in vivo. Additionally, we found frequent PD-L1/PD-L2 SVs in virus-associated lymphomas by targeted sequencing. These findings not only reveal a novel regulatory machinery of PD-L1/PD-L2 expression, but also provide a possibility that PD-L1/PD-L2 3′-UTR disruption can serve as a biomarker for immune checkpoint therapy

日時：２０１９年６月１０日（月） １６：００〜１７：００

場所：吉田記念講堂

連絡先：後藤 理（内線５６１１）

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