Investigation of the molecular behavior and the therapeutic strategy regarding thymoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19975
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory surgery
• Research Institution: Nagoya University
• Principal Investigator: Hakiri Shuhei 名古屋大学, 医学部附属病院, 病院助教 (40647476)
• Research Collaborator: FUKUI Takayuki ; KATO Taketo ; MORI Shunsuke
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 胸腺腫 / 胸腺上皮性腫瘍 / 免疫チェックポイント阻害剤 / PD-L1 / PD-1

Outline of Final Research Achievements

Programmed death ligand 1 (PD-L1) is reportedly expressed in various malignancies and is considered a prognostic factor. We attempted to reveal
the usefulness of the PD-L1 expression as a prognostic factor in patients with thymoma. Eighty-one patients with thymoma who underwent surgical resection between 2004 and 2015 were retrospectively reviewed. The PD-L1 expression was
evaluated by immunohistochemistry and stratified by the proportion of positive tumor cells. Strong membranous reactivity of the PD-L1 antibody in 1% or more of tumor cells was considered “positive.” The association between the PD-L1 expression and the clinicopathologic features was investigated. The PD-L1 expression was positive in 22 patients (27%) and negative in 59 patients (73%). The PD-L1 positivity was significantly associated with type B2 and B3 thymoma and stage III and IV disease. In addition, PD-L1 positive tumors showed a significantly higher maximum standardized uptake value than PD-L1 negative tumors.

Free Research Field

胸部外科

Academic Significance and Societal Importance of the Research Achievements

近年、PD-1、PD-L1を標的とした免疫チェックポイント阻害剤が各種悪性腫瘍で保険適応となった。胸部外科領域では肺癌において数種類の免疫チェックポイント阻害剤が臨床導入され、進行肺癌に対する治療の選択肢となり、これまでの大規模臨床試験において、肺癌のPD-L1発現が予後不良で、免疫チェックポイント阻害剤の治療効果にも影響を及ぼす可能性が示唆された。一方で稀少な悪性腫瘍である胸腺腫で免疫治療に関する報告は少ない。本研究において我々は胸腺腫におけるPD-L1発現と臨床組織的な特徴、予後との関係を調べ、胸腺腫に対する免疫チェックポイント阻害剤を用いた新たな治療戦略の基礎データを示した。