Immunogenomic profile associated with response to neoadjuvant chemoradiotherapy in patients with rectal cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08664
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: AKIYOSHI Takashi 公益財団法人がん研究会, 有明病院 大腸外科, 副部長 (50625598)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 直腸癌 / 術前放射線化学療法 / 免疫ゲノム解析

Outline of Final Research Achievements

The significance of T-cell complexity in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) remains unknown. High-throughput T-cell receptor (TCR) β sequencing was applied to quantify the TCR repertoire of pre-treatment biopsies from 67 patients with advanced rectal cancer receiving preoperative CRT. Diversity index was used to represent the complexity of the TCR repertoire in a tumor. Changes in TCR repertoire before and after CRT were also analyzed in 23 patients. Diversity indices were significantly higher for good responders than for non-responders. Larger changes in TCR repertoires before and after CRT were correlated with better recurrence-free survival. The complexity and dynamic change in the TCR repertoire might serve as a useful indicator of response to CRT in patients with rectal cancer.

Free Research Field

大腸外科

Academic Significance and Societal Importance of the Research Achievements

腫瘍浸潤CD8陽性T細胞の密度が直腸癌に対する術前化学放射線療法(CRT)の治療効果と相関することはこれまで報告されていたが、本研究でははじめて腫瘍浸潤CD8陽性T細胞の密度だけでなくT細胞レパトアの多様性がCRTの治療効果の予測に有用であることを示した。