Interrogating BDCA3+ dendritic cells in human tumor-draining lymph nodes (127.43)

Abstract

Human blood dendritic cells (DCs) expressing BDCA3 (CD141) have been characterized and described by several groups to represent the human counterpart of the mouse cross-presenting CD8α+ DC. Fully functional cross-presenting DCs are of utmost importance for the induction of tumor-antigen specific CD8 T-cell responses. In the current study, we set out to interrogate BDCA3+ DC within human tumor-draining lymph nodes (LNs) from melanoma and breast cancer patients. For this purpose a 12-color polychromatic flow panel for human DC was developed. CD11c+BDCA3+ cells were found to be of immature phenotype (low in CD80, CD86 and CD83) upon isolation. When comparing a group of 9 tumor-negative LNs with 4 tumor-positive LNs of BrCa patients, the percentage of CD11c+BDCA3+ cells was significantly higher (p<0.03) in the specimen containing tumor metastasis. Moreover, when comparing the activation status of BDCA3+ cells in LNs from advanced melanoma patients that did or did not grossly display evidence of metastatic disease, we observed lower expression of the DC maturation marker CD83 in the grossly positive LNs, suggesting that this population of DC might be affected by active tumor-induced suppression. In ongoing studies we are sorting these BDCA3+ DC to determine their cross-presenting abilities and to determine whether a (tumor-induced) immature phenotype is also reflected in the functional capabilities of these cells.