title: The effects of chemotherapeutic drugs on human monocyte-derived dendritic cell differentiation and antigen presentation.
abstract: Recent studies indicate that chemotherapeutic agents may increase the anti-tumoral immune response. Based on the pivotal role of dendritic cells (DCs) in host tumour-specific immune responses, we investigated the effect of commonly used chemotherapeutic drugs dexamethasone, doxorubicin, cisplatin and irinotecan and glucocorticoids on monocyte-derived DCs (moDCs). Dexamethasone displayed the strongest inhibitory effect on DC differentiation. The effect of cisplatin and irinotecan was moderate, while only weak effects were noticed for doxorubicin. Surprisingly, when the functional consequence of chemotherapy-treated CD14(+) monocytes and their capacity to activate CD4(+) T responders cells were investigated, cisplatin-treated monocytes gave rise to increased T cell proliferation. However, dexamethasone, doxorubicin and irinotecan-pretreated monocytes did not stimulate any increased T cell proliferation. Further investigation of this observation revealed that cisplatin treatment during DC differentiation up-regulated significantly the interferon (IFN)-β transcript. By contrast, no effect was evident on the expression of interleukin (IL)-1β, tumour necrosis factor (TNF)-α, IL-6 or IFN-α transcripts. Blocking IFN-β attenuated the cisplatin-enhanced T cell proliferation significantly. In conclusion, cisplatin treatment enhanced the immune stimulatory ability of human monocytes, a mechanism mediated mainly by the increased production of IFN-β.
authors.affiliation: Department of Medicine, Translational Immunology Unit, Karolinska Institute, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Hu
authors.forename: J
authors.initials: J
authors.lastname: Kinn
authors.forename: A A
authors.initials: AA
authors.lastname: Zirakzadeh
authors.forename: A
authors.initials: A
authors.lastname: Sherif
authors.forename: G
authors.initials: G
authors.lastname: Norstedt
authors.forename: A-C
authors.initials: AC
authors.lastname: Wikström
authors.forename: O
authors.initials: O
authors.lastname: Winqvist
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D007167:Immunotherapy; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D000077146:Irinotecan; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D012333:RNA, Messenger; D000077146:Irinotecan; D016899:Interferon-beta; D003907:Dexamethasone; D004317:Doxorubicin; D002945:Cisplatin; D002166:Camptothecin