Role of mast cell in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08645
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: The University of Tokushima
• Principal Investigator: NISHI Masaaki 徳島大学, 病院, 助教 (70464344)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肥満細胞 / 大腸癌 / 放射線化学療法 / 腫瘍微小環境

Outline of Final Research Achievements

We aimed to examine the correlation between mast cell (MC) infiltration and neoadjuvant chemoradiotherapy (nCRT) response for locally advanced rectal cancer (LARC). Protein levels of the MC marker tryptase and tumor-associated macrophages (TAMs) marker CD206 were evaluated with immunohistochemistry (IHC). The effects of MCs on the malignant potential were examined using in vitro assays with a colorectal cancer (CRC) cell line. By tryptase IHC analysis. MC infiltration was significantly correlated with nCRT response. The 5-year DFS rate was significantly lower in the MC-positive group. MC infiltration was the independent prognostic indicator. MC infiltration was significantly correlated with CD206 expression. In vitro experiments suggested that tumor activated mast cells could promote CRC malignant behavior via production of macrophage inhibitory factor. MC infiltration in LARC patients was positively correlated with TAM infiltration and resistance to nCRT.

Free Research Field

消化器外科学、腫瘍微小環境、放射線化学療法

Academic Significance and Societal Importance of the Research Achievements

下部直腸癌症例における肥満細胞（Mast cell：MC）浸潤は術前化学放射線療法CRTの治療抵抗性、Tumor associated macrophage(TAM)TAMの浸潤と正の相関を示し、DFSにおいて独立予後不良因子であった。MCはCRT抵抗性直腸癌の新たな治療のtargetになりうる。腫瘍微環境構築の根幹となる肥満細胞をtargetとした難治性癌の治療戦略確立を目指すことは社会的にも意義のあることであり、癌人口が増加の一途をたどる現状を考慮すると、腫瘍微小環境攻略の糸口となる治療法開発による学術的、臨床的、経済的恩恵は計り知れないと考えられる。