Novel peritoneal seeding therapy using NKT cell activation vector focused on anti-PD-1 antibody resistance mechanism

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17650
• 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: Sugita Yutaka 神戸大学, 医学研究科, 医学研究員 (70802346)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 腹膜播種 / 抗PD-1抗体 / MDSC / NKT細胞

Outline of Final Research Achievements

The tumor microenvironment is composed not only of tumor cells, but also of various immune cells and stromal cells. Among them, Myeloid-derived suppressor cells (MDSCs) are suppressor immune cells and are involved in the establishment of the tumor microenvironment. On the other hand, there have been few reports on peritoneal seeding, and the studies are still insufficient. In this study, we created a mouse model of peritoneal dissemination of colorectal cancer, analyzed the dynamics of intraperitoneal MDSCs, and examined their involvement in the pathogenesis of peritoneal dissemination. The results showed that intraperitoneal MDSCs increased with disease progression after intraperitoneal administration of MC38. The proportion of PMN-MDSCs increased especially in the peritoneal cavity. Anti-Ly6G antibody-induced MDSC disappearance studies inhibited tumor progression.

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Free Research Field

癌免疫

Academic Significance and Societal Importance of the Research Achievements

腹膜播種は胃癌の再発形式の45%を占め、死因の約60%は腹膜播種に伴う癌性腹膜炎とされているが、未だ有効な治療法がなく予後不良である。腹膜播種は抗PD-1抗体に効果が乏しいとされており、その新たな治療戦略の開発が必要である。研究提案者は腹膜播種の病態 に腹腔内骨髄由来抑制細胞(MDSC)が関与することを明らかにした腹膜播種の病態には腹腔内G-MDSCが強く関連することを見出した。MDSCを標的にした新たな治療の開発はCD8＋T細胞などの抗腫瘍免疫を活性化することで、腹膜播種の治療に活路を見出すことを可能とする。