DENDRITIC CELLS IN BARRETT’S ESOPHAGUS CARCINOGENESIS: AN INADEQUATE MICROENVIRONMENT FOR ANTITUMOR IMMUNITY?

in American Journal of Pathology (in press)

Dendritic cells in Barrett's carcinogenesis: an inadequate environment for antitumor immunity?

Conference (2013)

Barrett's metaplasia, dysplasia and esophageal ademnocarcinoma: an inadequate antitumour immunity?

Conference (2012, February 09)

Production of large numbers of plasmacytoid dendritic cells with functional activities from CD34+ hematopoietic progenitor cells: use of IL-3

Poster (2011, December)

Implication of plasmacytoid dendritic cells in the malignant transformation of cervical epithelial metaplasia

Poster (2010, September)

The cervical transformation zone is a dynamic area of a few millimeters in which a glandular epithelium has been replaced by a squamous epithelium through a metaplastic process. Interestingly, a ... [more ▼]

The cervical transformation zone is a dynamic area of a few millimeters in which a glandular epithelium has been replaced by a squamous epithelium through a metaplastic process. Interestingly, a substantial majority (87%) of cervical (pre)cancerous lesions develops within this peculiar microenvironment. Our previous studies reported that intrinsic immune features altered in the metaplastic epithelium could contribute to cancer development by preventing efficient antitumor/antiviral immune response. Plasmacytoid dendritic cells (pDC) are key effectors in host innate immunity and orchestrate adaptive immune responses. Recently, infiltration by these subtypes of dendritic cells has been shown in different cancers. However their implication in antitumor response is largely debated. The present study was performed to determine the implication of pDC in the cervical “metaplasia-dysplasia-cancer” sequence. We demonstrated that the density of pDC increases in the epithelium of metaplastic and (pre)cancerous cervical tissues as well as in underlying stroma as compared with normal exocervical epithelium. This could be partially explained by the increased expression of chemerin, their chemotactic peptide, observed in those areas. We developed a method to efficiently generate pDC cells exhibiting morphological and immunohistochemical features of blood pDC from a limited number of CD34+ cord blood progenitors. Using these in vitro generated pDC, we demonstrated that medium conditioned by transformed keratinocytes modified the activation status of pDC, by inducing a decreased expression of costimulatory molecules such as CD86 and HLA-DR. Moreover, malignant keratinocytes diminished the ability of pDC to produce IFNα in response to an oligonucleotide containing CpG motifs, a defined microbial stimulus for pDC. These results suggest that pDC could be educated within the metaplastic and/or (pre)cancerous microenvironment to acquire a tolerogenic phenotype that could promote carcinogenesis. In agreement with those results, we observed that both metaplastic areas and (pre)cancerous lesions of the cervix are infiltrated by T regulatory cells. [less ▲]

High expression of PGE2 enzymatic pathways in cervical (pre)neoplastic lesions and functional consequences for antigen-presenting cells

in Cancer Immunology, Immunotherapy (2009), 58(4), 603-614

Increased migration of Langerhans cells in response to HPV16 E6 and E7 oncogene silencing: role of CCL20

in Cancer Immunology, Immunotherapy (2009), 58(1), 39-47

TCRγδ cells in HPV-associated cervical cancer

in Acta Clinica Belgica (2008), 63