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The effects of chemotherapeutic drugs on human monocyte-derived dendritic cell differentiation and antigen presentation
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
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2013 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 172, no 3, 490-499 p.Article in journal (Refereed) Published
Abstract [en]

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)- transcript. By contrast, no effect was evident on the expression of interleukin (IL)-1, tumour necrosis factor (TNF)-, IL-6 or IFN- transcripts. Blocking IFN- 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-.

Place, publisher, year, edition, pages
2013. Vol. 172, no 3, 490-499 p.
Keyword [en]
antigen presentation, chemotherapeutic drugs, cisplatin, dendritic cell, immunotherapy
National Category
Medical and Health Sciences
URN: urn:nbn:se:umu:diva-71582DOI: 10.1111/cei.12060ISI: 000318073000015OAI: diva2:625869
Available from: 2013-06-05 Created: 2013-06-04 Last updated: 2013-06-05Bibliographically approved

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Sherif, Amir
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