Lymph node invasion by tumor cells modify the distribution of dendritic cells subsets in human cancer patients

NICOLÁS NÚÑEZ; PÉROL, LOUIS; ANA TEREZA NADAN; SASTRE-GARAU X; DE LA ROCHERE P; VIEL S; SEDLIK C; AMIGORENA S; PIAGGIO E

Simposio; DC2014 : 13th International Symposium on Dendritic Cells; 2014

In human breast cancer the invasion of tumor draining lymph nodes (TDLNs) is an important step in disease progression and it has a predictive value. Dendritic cells (DCs) are a heterogeneous population of professional antigen-presenting cell that initiate adaptive immune responses in lymph nodes (LNs). These cells comprise several subsets that can be identified based on phenotypic markers. In human TDLNs, several DC subsets have been recently identified, including lymphoid-organ-resident and migratory DCs. Skin-derived migratory DCs include Langerhans cells (LCs), dermal CD1a+ and CD206 DCs; and blood- derived resident DCs include plasmacytoid (pDCs), Clec9a+ and BDCA1+ DCs. We hypothesized that the distribution of the different DCs subset as well as their activation patterns could be influenced by the presence of tumor cells in TDLNs. To address this hypothesis we characterized by FACS the different DC subpopulations present in non-invaded TDLN (NI) and invaded (INV) breast cancer draining LNs. We did not observe any differences in the percentages of pDCs, and CD1a+ cells present in NI vs INV LNs. However, we found a decrease in the percentages of BDCA1+ DCs and a significant increase in the percentage of CD14+ cells in INV LNs, which also show a more activated phenotype. These results suggest that the presence of breast tumor cells in TDLNs modifies the DC subset distribution and this modification could be at the origin of changes in the normal initiation of the adaptive immune response against tumors.