PT  - JOURNAL ARTICLE
AU  - Perrot, Ivan
AU  - Blanchard, Dominique
AU  - Freymond, Nathalie
AU  - Isaac, Sylvie
AU  - Guibert, Benoît
AU  - Pachéco, Yves
AU  - Lebecque, Serge
TI  - Dendritic Cells Infiltrating Human Non-Small Cell Lung Cancer Are Blocked at Immature Stage
AID  - 10.4049/jimmunol.178.5.2763
DP  - 2007 Mar 01
TA  - The Journal of Immunology
PG  - 2763--2769
VI  - 178
IP  - 5
4099  - http://www.jimmunol.org/content/178/5/2763.short
4100  - http://www.jimmunol.org/content/178/5/2763.full
SO  - J. Immunol.2007 Mar 01; 178
AB  - 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-α. 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.