Dendritic cell infiltration and prognosis of early stage breast cancer

Purpose: Although dendritic cells (DC) and T cells can infiltrate primary breast carcinoma, it remains unclear whether the immune response influences the clinical outcome. Experimental Design: T lymphocytes and DC infiltration within primary tumors was investigated in 152 patients with invasive nonmetastatic breast cancer. CD1a, CD3, CD68, CD123, CD207/Langerin, and CD208/DC-LAMP expression was assessed with semiquantitative immunohistochemical analysis. Expression of chemokines involved in DC migration (MIP-3a/CCL20, MIP-3b/CCL19, and 6Ckine/ CCL21) was also examined. The correlation between these markers and the characteristics of the tumors, as well as relapse-free and overall survival was analyzed. Significant prognostic parameters were then tested in a validation series. Results: Infiltration by immature CD207/Langerin' DC was found in a third of the cancers and did not correlate with clinicopathological data. Presence of mature CD208/DCLAMP(+) DC (56%) and CD3+ T cells (82%) strongly correlated with lymph node involvement and tumor grade. Among the chemokines analyzed, only the presence of MIP-3b/CCL19 in 57% of the tumors correlated with prolonged overall survival. CD123(+) plasmacytoid DC (pDC) infiltrated 13% of the primary tumors. Their presence was strongly associated with shorter overall survival (93% versus 58% at 60 months) and relapse-free survival (90% versus 37% at 60 months) and was found to be an independent prognostic factor for overall survival and relapse-free survival and confirmed in an independent validation series of 103 patients. Conclusions: Infiltration by pDC of primary localized breast tumor correlates with an adverse outcome, suggesting their contribution in the progression of breast cancer.