In Breast Carcinoma Tissue, Immature Dendritic Cells Reside within the Tumor, Whereas Mature Dendritic Cells Are Located in Peritumoral Areas

TLDR

High macrophage inflammatory protein 3α expression by breast carcinoma cells likely drives the accumulation of immature dendritic cells within the tumor. Immunohistochemistry identified immature DCs (CD1a⁺/Langerin⁺/MHC II⁺) and mature DCs (CD83⁺/DC‑Lamp⁺) in breast carcinoma tissue, with tumor cells defined by morphology and cytokeratin. All tumors contained immature DCs within the tumor bed, whereas mature DCs were confined to peritumoral regions in 20/32 cases, with immature DCs adhering to tumor cells and mature DCs forming peritumoral DC‑T cell clusters.

Abstract

We have analyzed the presence of immature and mature dendritic cells (DCs) within adenocarcinoma of the breast using immunohistochemistry. Immature DCs were defined by expression of CD1a-, Langerin-, and intracellular major histocompatibility complex class II-rich vesicles. Mature DCs were defined by expression of CD83 and DC-Lamp. Breast carcinoma cells were defined by morphology and/or cytokeratin expression. We demonstrate two levels of heterogeneity of DCs infiltrating breast carcinoma tissue: (a) immature CD1a(+) DCs, mostly of the Langerhans cell type (Langerin(+)), were retained within the tumor bed in 32/32 samples and (b) mature DCs, CD83(+)DC-Lamp(+), present in 20/32 samples, are confined to peritumoral areas. The high numbers of immature DCs found in the tumor may be best explained by high levels of macrophage inflammatory protein 3alpha expression by virtually all tumor cells. Confirming the immature/mature DC compartmentalization pattern, in vitro-generated immature DCs adhere to the tumor cells, whereas mature DCs adhere selectively to peritumoral areas. In some cases, T cells are clustering around the mature DCs in peritumoral areas, thus resembling the DC-T cell clusters of secondary lymphoid organs, which are characteristic of ongoing immune reactions.