Elucidation of immune evasion mechanism and development of novel immunotherapy for esophageal squamous cell carcinoma for development of innovative immunotherapy

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16477
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kumamoto University
• Principal Investigator: Toihata Tasuku 熊本大学, 病院, 特任助教 (60879881)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 腫瘍免疫 / 食道癌 / 免疫チェックポイント

Outline of Final Research Achievements

It took an enormous amount of time to prepare paraffin-embedded sections of 495 resected specimens.
Mutations, amplifications, and deletions were analyzed from the information obtained by Exome analysis using unstained molecular markers and DNA collected by laser microdissection (Software; Mutect2, GISTIC analysis, etc.). Genetic alterations in cancer cells that correlate with the extracted immune factors are extracted and detected by real-time PCR in 495 cases. Integrate analysis of mutually correlated immunological factors and genetic alterations of cancer cells in esophageal squamous cell carcinoma with clinical data in 495 cases to elucidate tumor immune evasion mechanisms in esophageal squamous cell carcinoma, which have not been clarified so far.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

腫瘍免疫微小環境の解明は、近年、世界中で注目を集めている先端性の高い分野であり、我々も食道癌におけるPD-L1の発現と食道癌の予後に関与することを報告した(Yagi et al. Ann Surg. 2019)。治療としては、抗PD-1阻害剤の適応疾患も拡大しており、特にMSI-Hの固形腫瘍に対して適応になったことは初めての臓器横断的な適応となり、腫瘍の免疫学的特性をより細分化し治療効果を予測することの重要性が増してきていることを示している[TCGA, Nature. 2014, 2017]。このように腫瘍の免疫微小環境を解明することが新たな治療法の開発の一助となることが予想され注目に値する。