T-Cell Receptor repertoire analyses in patients with esophageal cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10488
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Tohoku University
• Principal Investigator: Mori Takahiro 東北大学, 医学系研究科, 教授 (00323030)
• Co-Investigator(Kenkyū-buntansha): 安田 純 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), 発がん制御研究部, 部長 (00281684) ; 齋藤 さかえ 東北大学, 東北メディカル・メガバンク機構, 講師 (20335491)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 食道癌 / 化学放射線療法 / 腫瘍免疫 / 予後予測因子

Outline of Final Research Achievements

We analyzed TCR repertoire in patients with esophageal cancer who had been treated by chemoradiation (CRT). In 68 cases, genomic DNAs extracted from peripheral white blood cells were used for TCR repertoire. The obtained results suggested that cases with high TCR clonality have better prognosis. In 4 cases who had been treated primarily by CRT followed by surgery, mRNA extracted from tumors and normal mucosal tissues were used for repertoire analyses. The obtained results suggested that some T cell clones are shared both in tumors and mucosal tissues, which may represent Tumor Infiltrating Lymphocytes (TIL), and cases with less TILs had poor prognosis. Besides, cases after CRT had high clonality of TCR within tumors as compared to a case with surgery alone. These results suggested that tumor immunity should play an important role in CRT for esophageal cancers and that TCR repertoire could be prognostic marker candidate.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

化学放射線療法（CRT）を施行された食道癌患者で腫瘍部と正常粘膜部に共通するユニークなT細胞クローンが存在すること（腫瘍への浸潤が少ないもので予後が８．５か月と不良）、末梢血でのクローナリティの高い症例ではCRT後の予後が良好であることが示唆された（p=0.103）。手術先行に比較してCRT後の切除例にクローナリティの高いという結果が得られた（Shannon 3.12±0.47, Simpson 14.9±5.77 ; 手術先行例ではShannon 5.72, Simpson 97.3）。このように、CRTの治療効果には腫瘍免疫が関与しており、本研究がCRTの予後予測に貢献できると考える。