Lymph Node Invasion by Tumor Cells Modifies the Distribution and Phenotype of Dendritic and T Cell Subsets in Breast Cancer Patients

NICOLÁS NÚÑEZ; ANA TEREZA NADAN; SEGURA ELODIE; PÉROL, LOUIS; MILDER, MAUDE; VIEL S; DE LA ROCHERE P; LOIRAT D.; MESEURE D; AMZALLAG N; SASTRE-GARAU X; SEDLIK C; AMIGORENA S; PIAGGIO E

Simposio; Kestoyne Symposia. Tumor Immunology. Alberta, Canada; 2015

In human breast cancer the invasion of tumor draining lymph nodes (TDLNs) contributes to disease progression and has predictive value. TDLNs dendritic cells (DCs) present tumor antigens to naïve T cells and induce their polarization into different functional subsets (Th1, Th2, regulatory T cells (Treg) ...) leading to antitumor T cell responses or to tolerance. Here, we compared the immune profile of 70 untreated luminal breast cancer Invaded (I) versus Non-invaded (NI) TDLNs, with the aim to identify immunomodulatory mechanisms associated with the presence of the metastatic tumor cells. We studied by multi-color flow cytometry the distribution of 6 different DC subpopulations and observed in I TDLNs a significant decrease in the percentage of BDCA1+ DCs (P < 0.05) and a significant increase in the percentage of CD11c+HLADR+CD14+ cells (P < 0.01), including macrophages and inflammatory DCs, compared to NI TDLNs (P < 0.05). We also found a significant lower frequency of naïve conventional cells in I TDLNs (P < 0.05). Both, in NI and I TDLNs, memory conventional and Treg cells were highly polarized, mainly to the Th1, but also to the Th2, Th17, Tfh and Th22 phenotypes, as determined by chemokine receptors and transcription factor expression. Further functional analysis showed that after ex-vivo PMA/Iono stimulation, the Th1-polarized conventional T cells, but not the Th1-polarized Tregs produced high amounts of IFN-γ, being the IFN-γ production significantly higher in I TDLNs (P < 0.05). Overall, we observed that immune cells with tolerogenic potential (Tregs, macrophages) and effector CD4+ and CD8+ T cells from I TDLNs, all show evidence of high activation. These results potentially explain the power of immunotherapies targeting the former ones that unleash the anti-tumor activity of the highly activated effector T cells.