Novel immunological tolerance in zebrafish of human cancer cell xenotransplants and cancer immunotherapy mechanisms

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670127
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Mie University
• Principal Investigator: TANAKA TOSHIO 三重大学, 医学(系)研究科(研究院), 教授 (00135443)
• Co-Investigator(Kenkyū-buntansha): NISHIMURA Yuhei 三重大学, 大学院医学系研究科・薬理ゲノミクス, 准教授 (30303720) ; SHIMADA Yasuhito 三重大学, 大学院医学系研究科・薬理ゲノミクス, 助教 (40378427) ; UMRMOTO Noriko 三重大学, 大学院医学系研究科・薬理ゲノミクス, 助教 (40649365)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: Zebrafish / cance / xenotransplantation / immunological tolerance / RNA-seq

Outline of Final Research Achievements

Immune suppression in host animals is an essential precondition for xenograft success because the host immune system has a tendency to reject implanted cancer cells. We developed a novel zebrafish model based on two-round cancer cell xenotransplantation that achieved cancer-specific immunological tolerance without immunosuppression. We irradiated human cancer cells to abolish their proliferative abilities and implanted them into young zebrafish. These cells lasted for 2 weeks. Three months after the first xenotransplantation, the same zebrafish were implanted with nonirradiated cell lines. These cancer cells proliferated and exhibited metastasis without immune suppression. We conducted dual RNA-seq of the tumour with its surrounding tissues and identified several regulatory genes in zebrafish that are involved in immunity were altered with immunotolerance. In conclusion, this xenograft method has potential as a platform for anti-cancer drug discovery.

Free Research Field

薬理ゲノミクス