Molecular machineries of antitumor immune responses triggered by anticancer chemotherapy

2014 Fiscal Year Final Research Report

• Project/Area Number: 23501283
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor immunology
• Research Institution: Hokkaido University
• Principal Investigator: JINUSHI Masahisa 北海道大学, 遺伝子病制御研究所, 准教授 (40318085)
• Co-Investigator(Kenkyū-buntansha): YOSHIYAMA Hironori 北海道大学, 遺伝子病制御研究所, 准教授 (10253147)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: 癌 / 免疫 / 腫瘍ミエロイド細胞 / TIM-3 / TIM-4 / HMGB1 / オートファジー / 抗がん剤

Outline of Final Research Achievements

Anticancer agents modulate host immune responses through various regulatory mechanisms. By screening the critical factors that increase upon anticancer therapies and regulate the immune responses by tumor-associated myeloid cells (TAM), ｗe identified several key factors expressed on TAM, which greatly influence antitumor effects of chemotherapy. For example, TIM-3 interacts with HMGB1 released from chemotherapy-treated tumor cells, and suppresses innate pattern recognition signals mediated by nucleic acids. On the other hands, DAMP released from chemotherapy-damaged tumors induced TIM-4 on TAM. TIM-4 promotes the autophagy-mediated lysosomal degradation of ingested tumors and represses antigen presentation and tumor-specific CTL responses.Our findings provide new evidences that targeting of TAM-derived factors provides new strategy to improve the therapeutic responses to anticancer regiments and eradicate therapy-resistant tumors.

Free Research Field

腫瘍免疫