defects in innate immunity render breast cancer initiating cells permissive to oncolytic adenovirus先天免疫缺陷使乳腺癌启动细胞的溶瘤腺病毒.pdfVIP

Defects in Innate Immunity Render Breast Cancer Initiating Cells Permissive to Oncolytic Adenovirus 1,2 1,2 3 1,2 1,2 Laura Ahtiainen *, Cristina Mirantes , Tiina Jahkola , Sophie Escutenaire , Iulia Diaconu , Pamela ¨ 4, Anna Kanerva1,5, Vincenzo Cerullo1,2, Akseli Hemminki1,2* Osterlund 1Transplantation Laboratory, Cancer Gene Therapy Group, Molecular Cancer Biology Program, Haartman Institute and Finnish Institute of Molecular Medicine, University of Helsinki, Helsinki, Finland, 2 HUSLAB, Helsinki University Central Hospital, Helsinki, Finland, 3 Department of Plastic Surgery, Helsinki University Central Hospital, Helsinki, Finland, 4 Viral Infections Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland, 5 Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland Abstract Background: Cancer stem cells/initiating cells (CSC/CIC), are thought to exist as a small population in malignant tissues. They are resistant to conventional cancer treatments and possibly underlie post-treatment relapse. The CIC population can be targeted with capsid modified oncolytic adenoviruses. Methodology/Principal Findings: We studied the mechanisms of innate immunity to oncolytic adenovirus Ad5/3-Delta24 in conventional treatment resistant non-CIC breast cancer cells, breast cancer CD44+/CD24 2/low CIC population and normal breast tissue CD44+/CD24 2/low stem cells. We compared virus recognition by pattern recognition receptors for adenovirus, Toll-like receptors (TLR) 2 and 9 and virus induced type I interferon (IFN) response regulation in these cell types. We show TL