Infiltrating dendritic/Langerhans cells in primary breast cancer

It is fully anticipated that dendritic cells (DCs) will become a mainstay for inclusion in biological therapies for patients with cancer including breast cancer. To elucidate the cellular composition of DCs infiltrating human breast cancers, we investigated the correlations between the density of infiltrating DCs and some clinicopathological factors of breast cancer patients, examined cytokine expression on cancer cells and finally, assessed the numbers of CD45RO(+) tumor infiltrating lymphocytes (TIL). Tissues adjacent to cancer nests contained significantly more S-100 protein(+) and S-100 protein(+) CD1a(-) DCs, but less CD1a(+) DCs, than the nests. In invasive ductal carcinomas infiltration by S-100 protein(+) DCs within and adjacent to nests, CDla(+) DCs within nests and S-100 protein(+) CD1a(-) DCs adjacent to nests was denser than that in non-invasive carcinomas. With respect to the histological subtypes, there were fewer DCs in scirrhous carcinomas. Patients with stage IV disease had significantly fewer DCs of primary lesions than at other clinical stages. There were good correlations between infiltration by S-100 protein(+) DCs and expression of the cytokines GM-CSF, IL-1 alpha and TNF-alpha on cancer cells and between GM-CSF expression and S-100 protein(+) CD1a(-) DCs. There was a close correlation between CD45RO(+) TIL and S-100 protein(+) DC densities both within and adjacent to the cancer nests and the S-100 protein(+) CD1a(-) DC density adjacent to the cancer nests. Despite extensive immunoelectron microscopic observation, CD1a(+) DCs within cancer nests contained only few Birbeck's granule-like structure. These data indicate that cancer nests are infiltrated predominantly by CD1a(+) DCs, whereas S-100 protein(+) CD1a(-) DCs predominate in surrounding tissues, and a infiltration by DCs may require cytokine expression on cancer cells and simultaneous lymphocyte infiltration. The findings of this clinicopathological study indicate the importance of evaluating simultaneously the types and localizations of infiltrating DCs in cancer tissues.