The Journal of Experimental Medicine
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Published online May 29, 2007
doi:10.1084/jem.20070021
The Journal of Experimental Medicine, Vol. 204, No. 6, 1441-1451
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Stary et al.
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ARTICLE

 Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells

Georg Stary1, Christine Bangert1, Martina Tauber2, Robert Strohal3, Tamara Kopp1, and Georg Stingl1

1 Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, 1090 Vienna, Austria
2 Department of Pathology and 3 Department of Dermatology, Federal Academic Hospital Feldkirch, 6800 Feldkirch, Austria

CORRESPONDENCE Georg Stingl: georg.stingl{at}meduniwien.ac.at

Imiquimod (IMQ), a synthetic agonist to Toll-like receptor (TLR) 7, is being successfully used for the treatment of certain skin neoplasms, but the exact mechanisms by which this compound induces tumor regression are not yet understood. While treating basal cell carcinoma (BCC) patients with topical IMQ, we detected, by immunohistochemistry, sizable numbers of both myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) within the inflammatory infiltrate. Surprisingly, peritumoral mDCs stained positive for perforin and granzyme B, whereas infiltrating pDCs expressed tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). The biological relevance of this observation can be deduced from our further findings that peripheral blood–derived CD11c+ mDCs acquired antiperforin and anti–granzyme B reactivity upon TLR7/8 stimulation and could use these molecules to effectively lyse major histocompatibility complex (MHC) class Ilo cancer cell lines. The same activation protocol led pDCs to kill MHC class I–bearing Jurkat cells in a TRAIL-dependent fashion. While suggesting that mDCs and pDCs are directly involved in the IMQ-induced destruction of BCC lesions, our data also add a new facet to the functional spectrum of DCs, ascribing to them a major role not only in the initiation but also in the effector phase of the immune response.

Abbreviations used: APC, allophycocyanin; BCC, basal cell carcinoma; IMQ, imiquimod; iNOS, inducible NO synthase; mDC, myeloid DC; pDC, plasmacytoid DC; TLR, Toll-like receptor; TRAIL, TNF-related apoptosis-inducing ligand; TUNEL, Tdt-mediated dUTP-biotin nick-end labeling.

T. Kopp and G. Stingl contributed equally to this study.


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