Plasmacytoid Dendritic Cell (pDC) Infiltration Correlate with Tumor Infiltrating Lymphocytes, Cancer Immunity, and Better Survival in Triple Negative Breast Cancer (TNBC) More Strongly than Conventional Dendritic Cell (cDC)

SIMPLE SUMMARY: Dendritic cells (DC) represent a major antigen-presenting cell in the tumor immune microenvironment (TIME) and play an essential role in cancer immunity. Clinical relevance of plasmacytoid DC (pDC) and conventional DC (cDC) infiltration were studied in large patient cohorts using transcriptomic analyses. We found that high pDC was significantly associated with better survival in triple negative breast cancer (TNBC), but not cDC. High pDC TNBC tumors enriched immune and inflammation-related gene sets including IFN-γ signaling more strongly than cDC TNBC, which also enriched metastasis-related gene sets. pDC correlated with CD8(+) and CD4(+) memory T cells, and had a cytolytic activity score stronger than cDC in TNBC. High pDC TNBC were associated with a high fraction of anti-cancer immune cells and high expression of all the immune checkpoint molecules examined. For the first time, we found that pDC are correlated with immune response and survival in TNBC patients more strongly than cDC. ABSTRACT: Dendritic cells (DC) represent a major antigen-presenting cell type in the tumor immune microenvironment (TIME) and play an essential role in cancer immunity. Conventional DC (cDC) and plasmacytoid DC (pDC) were defined by the xCell algorithm and a total of 2968 breast cancer patients (TCGA and METABRIC) were analyzed. We found that triple-negative breast cancer (TNBC) had a high fraction of cDC and pDC compared to the other subtypes. In contrast to cDC, high pDC in TNBC was significantly associated with better disease-specific and disease-free survival consistently in both cohorts. High cDC TNBC tumors enriched not only inflammation and immune-related, but also metastasis-related gene sets in Gene Set Enrichment Analysis, whereas high pDC TNBC enriched inflammation and immune -related gene sets including IFN-γ signaling more strongly than cDC. pDC TNBC correlated with CD8(+), CD4(+) memory, IFN-γ score, and cytolytic activity stronger than cDC TNBC. High pDC TNBC were associated with a high fraction of anti-cancer immune cells and high expression of all the immune check point molecules examined. In conclusion, pDC levels correlated with the infiltration of immune cells and patient survival in TNBC more strongly than cDC; this is the first study suggesting the clinical relevance of pDC infiltration in TNBC.