2021 Fiscal Year Final Research Report

The influence of neoadjuvant chemoradiotherapy upon tumor microenvironment in pancreatic cancer

Research Project

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Project/Area Number	19K07670
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 50010:Tumor biology-related
Research Institution	Yokohama City University
Principal Investigator	ENDO Itaru 横浜市立大学, 医学研究科, 教授 (60211091)
Co-Investigator(Kenkyū-buntansha)	松山隆生横浜市立大学, 医学部, 准教授 (30464548) 本間祐樹横浜市立大学, 医学部, 講師 (60567618) 廣島幸彦地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), 臨床研究所, 医長 (60718021)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	膵癌 / 術前化学放射線療法 / 癌免疫 / 腫瘍関連マクロファージ / 性差
Outline of Final Research Achievements	This study aimed to investigate gender-dependent antitumor immune response to neoadjuvant chemoradiotherapy (NACRT) in pancreatic ductal adenocarcinoma (PDAC) patients. This study enrolled 58 patients with borderline resectable PDAC who underwent surgical resection after NACRT. The resected tumor specimens were analyzed for immune cells using immunohistochemical staining. The relationship between clinicopathological features and clinical outcomes was evaluated. Females had longer overall survival than males. The CD204+ TAM number was significantly lower in females than in males. IRF-5+ cell number was significantly higher in female patients. Negative correlation occurred between CD204+ cells and IRF-5-positive cells. Female gender was an independent prognostic factor possibly due to the greater reduction in CD204+ TAM infiltration in tumors after NACRT. The beneficial effects of NACRT on TAMs’ infiltration might be associated with gender-dependent IRF-5 expression.
Free Research Field	肝胆膵外科
Academic Significance and Societal Importance of the Research Achievements	膵癌は難治性癌の代表疾患である。根治が期待できる唯一の治療法は手術のみであるが、化学療法が予後改善に寄与することが分かってきた。化学療法の効果の一つとして、癌免疫賦活化作用が最近注目されている。本研究結果から、膵癌においても術前化学放射線療法が免疫賦活化に有効であることが考えられ、その効果には性差がある可能性が示唆された。術前治療が免疫応答に及ぼす影響と機序を解明することで、今後の新しい治療法の開発が期待出来ると考えられた。