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.
Skip Nav Destination
Article navigation
11 June 2007
Article|
May 29 2007
Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells
Georg Stary,
Georg Stary
1Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, 1090 Vienna, Austria
Search for other works by this author on:
Christine Bangert,
Christine Bangert
1Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, 1090 Vienna, Austria
Search for other works by this author on:
Robert Strohal,
Robert Strohal
3Department of Dermatology, Federal Academic Hospital Feldkirch, 6800 Feldkirch, Austria
Search for other works by this author on:
Tamara Kopp,
Tamara Kopp
1Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, 1090 Vienna, Austria
Search for other works by this author on:
Georg Stingl
Georg Stingl
1Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, 1090 Vienna, Austria
Search for other works by this author on:
Georg Stary
1Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, 1090 Vienna, Austria
Christine Bangert
1Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, 1090 Vienna, Austria
Martina Tauber
2Department of Pathology
Robert Strohal
3Department of Dermatology, Federal Academic Hospital Feldkirch, 6800 Feldkirch, Austria
Tamara Kopp
1Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, 1090 Vienna, Austria
Georg Stingl
1Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, 1090 Vienna, Austria
CORRESPONDENCE Georg Stingl: [email protected]
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.
Received:
January 02 2007
Accepted:
May 09 2007
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2007
J Exp Med (2007) 204 (6): 1441–1451.
Article history
Received:
January 02 2007
Accepted:
May 09 2007
Connected Content
Related
Tumor-killing DCs
Citation
Georg Stary, Christine Bangert, Martina Tauber, Robert Strohal, Tamara Kopp, Georg Stingl; Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells . J Exp Med 11 June 2007; 204 (6): 1441–1451. doi: https://doi.org/10.1084/jem.20070021
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
See also
Email alerts
Advertisement