Elucidation of tumor immune microenvironment after preoperative chemoradiotherapy for rectal cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17651
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kobe University
• Principal Investigator: Agawa Kyosuke 神戸大学, 医学部附属病院, 医員 (70870343)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 直腸癌 / 術前化学放射線療法 / CD8(+)T細胞

Outline of Final Research Achievements

A mouse colorectal cancer radiotherapy model was created to analyze CD8+ T cell kinetics and reproduce the increase in CD8+ T cells in the tumor. The cells were classified into three fractions according to the degree of exhaustion. PD-1+Tim3+CD8+ T cells were markedly increased, and IFN-γ production in that fraction was enhanced.
Next, to achieve highly accurate detection of TIME component cells in colorectal cancer, we created virtual slides by staining rectal cancer specimens after NACRT. These cells were then identified by AI. The results showed that the number of CD8+ T cells in the tumor was related to the recurrence rate and histological response.

Free Research Field

消火器外科

Academic Significance and Societal Importance of the Research Achievements

直腸癌に対する術前化学放射線療法(NACRT)で組織学的奏功度を得ることは、治療成績の向上につながる。病理学的完全奏功(pCR)は予後良好であり、患者にとって大いなる福音となるが、現実的には、標準治療とはならず、一つのオプションに止まる。実際、pCR率は20%未満と低いことが要因といえる。NACRT後の腫瘍内CD8+T細胞の動態を解析することで、術前治療のより有用なバイオマーカーの開発にもつながり、さらにAIを用いた解析は、革新的な技術で多くの情報を迅速かつ客観的に取得することが可能となると考え、pCR率の向上を目指すために学問的にも意義深いの研究である