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* Laboratory for Immunological Research, Schering-Plough, Dardilly, France; Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, France;
Department of Pneumology,
Department of Pathology, and
Department of Thoracic Surgery, and
¶ Institut National de la Santé et de la Recherche Médicale, Unité 503 and
|| Université Lyon 1, Lyon, France
The efficacy of immune response to control human cancer remains controversial. It is particularly debated whether and to what extent the capacity of tumor-infiltrating dendritic cells (DC) to drive immunization can be turned off by transformed cells, leading to tumor-specific tolerance rather than immunization. To address this issue, we have characterized the DC isolated from human non-small cell lung cancer (NSCLC). These biopsy specimens contained CD11chigh myeloid DC (mDC), but also CD11c– plasmacytoid DC (pDC) and a third DC subset expressing intermediate level of CD11c. Compared with peripheral blood, CD11chigh tumor-infiltrating DC (TIDC) displayed a "semi-mature" phenotype, and TLR4 or TLR8 stimulation drove them to mature partially and to secrete limited amounts of cytokines. In contrast, most tumor-infiltrating pDC were immature but underwent partial maturation after TLR7 activation, whereas TLR9 ligation triggered low secretion of IFN-
. CD11cint mDC represented 
25% of total DC in tumoral and peritumoral tissues and expressed low levels of costimulatory molecules contrasting with high levels of the immunoinhibitory molecule B7-H1. Finally, the poor APC function of total TIDC even after TLR stimulation and the migratory response of both tumor-infiltrating mDC and pDC toward CCL21 and SDF-1 in vitro suggested their ability to compromise the tumor-specific immune response in draining lymph nodes in vivo. Further studies will be required to establish the specific role of the three TIDC subsets in tumor immunity and to draw conclusions for the design of therapeutic strategies.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a grant from the Institut National du Cancer-Canceropole 2004–05.
2 Address correspondence and reprint requests to Dr. Serge Lebecque, Centre Hospitalier Lyon-Sud Service de Pneumologie, Bâtiment 5F, 165 chemin du Grand Revoyet, 69495 Pierre-Bénite, France. E-mail address: serge.lebecque{at}chu-lyon.fr
3 Abbreviations used in this paper: DC, dendritic cell; mDC, myeloid DC; pDC, plasmacytoid DC; TIDC, tumor-infiltrating DC; NSCLC, non-small cell lung cancer; PMC, pulmonary mononuclear cell; BDCA, blood DC Ag; SDF, stromal cell-derived factor; int, intermediate.
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