Analysis of interaction between gastric cancer cells and immune cells in Epstein-Barr virus associated gastric carcinoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07012
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Abe Hiroyuki 東京大学, 大学院医学系研究科(医学部), 講師 (40708632)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 胃癌 / 食道癌 / 腫瘍免疫 / Epstein-Barr virus / 神経内分泌細胞癌

Outline of Final Research Achievements

I analyzed tumor immune status in Epstein-Barr virus associated gastric cancer (EBVaGC) and neuroendocrine carcinoma (NEC). In EBVaGC, high viral copy number in a single tumor cell was associated with poor prognosis and frequent PD-L1 expression. Viral copy number is thought to be an important factor for tumor immune evasion in EBVaGC. However, in peritoneal dissemination of EBVaGC, the number of CD8-positive cells infiltrating in the tumor was small compared to the primary tumor, although the number of cases analyzed was small. Use of immune checkpoint therapy should be considered carefully in cases with peritoneal disseminations. Neuroendocrine carcinoma in the stomach and esophagus expressed PD-L1 in 60% to 70% cases. PD-1/PD-L1 pathway was thought as a potential therapeutic target in gastric and esophageal NEC.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

ウイルス感染を特徴とするEpstein-Barr virus関連胃癌(EBV胃癌)、及び予後不良で有効な治療標的が確立されていない神経内分泌細胞癌(Neuroendocrine carcinoma, NEC)を対象に、腫瘍免疫状態の解析を行った。その結果、EBV胃癌での腫瘍細胞内ウイルス量とPD-L1(腫瘍免疫回避に重要な分子)の発現が相関することが分かり、腫瘍免疫回避機構の一端を明らかにすることができた。また胃や食道に発生するNECは高頻度にPD-L1を発現しており、PD-L1が治療標的となり得ることが明らかとなった。