Analysis of antitumor immune activation via tumor cell-derived DNA

2016 Fiscal Year Final Research Report

• Project/Area Number: 15H05994
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: KITAI Yuichi 北海道大学, 薬学研究院, 助教 (90756165)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Keywords: がん免疫 / 抗がん剤 / 細胞死

Outline of Final Research Achievements

Danger-associated molecular patterns (DAMPs) derived from damaged or dying cells not only elicit inflammation but also potentiate antitumor immune responses. Here, we show that treatment of breast cancer cells with the antitumor agent Topotecan, an inhibitor of topoisomerase I, induces DAMP secretion that triggers dendritic cell (DC) activation and cytokine production. Topotecan administration inhibits tumor growth in tumor-bearing mice, accompanied by infiltration of activated DCs and CD8+ T cells. These effects are abrogated in mice lacking STING, an essential molecule in cytosolic DNA-mediated innate immune responses. Furthermore, Topotecan-treated cancer cells release exosomes that contain DNA, which activate DCs via STING signaling. These findings suggest that a STING-dependent pathway drives antitumor immunity by responding to tumor cell-derived DNA.

Free Research Field

自然免疫