Infiltrating dendritic/Langerhans cells in primary breast cancer

Abstract

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, CD1a+ 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-1alpha 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.

Role of tumor‐derived proinflammatory cytokines GM‐CSF, TNF‐α, and IL‐12 in the migration and differentiation of antigen‐presenting cells in cervical carcinoma

“…This is in agreement with the previously reported effect of GM-CSF on migration of LHC/DC into organotypic cultures of HPV-transformed keratinocytes. 30 A similar positive correlation between the presence of GM-CSF, TNF-a, and the number of mature DC in breast cancer tissue was reported by Tsuge et al 31 In contrast, Trutmann et al 32 did not report a significant association between expression of GM-CSF and number of mature DC in colorectal cancer. A high level of TNF-a is known to induce migration of LHC to peripheral lymph nodes.…”

CD1a-positive infiltrating-dendritic cell density and 5-year survival from human breast cancer

“…The finding that activation was low or absent in tumour-associated DC populations in most breast cancers may have some bearing on the lack of apparent statistical association between CD1a and S-100 expression and survival. The observations that activated, mature DCs were restricted to a peritumoural location rather than within the tumour (Bell et al, 1999;Tsuge et al, 2000) imply that regional The association between CD1a and the NPI shows a nonsignificant (P ¼ 0.486) trend. Note that 20% of the patients with a higher CD1a density had a high (unfavourable) NPI, while 80% of the patients with a low CD1a density had an unfavourable NPI.…”

“…These findings show that the antitumour immune response in breast cancer is ineffective and that deficient DC function, at least in part, may be responsible for this (Coventry et al, 1996;Gabrilovich et al, 1997). The maturity and location of DC within breast tumours may not be uniform, such that more mature DCs, expressing differentiation/activation markers such as CD83, have been noted to be located peritumourally around the tumour mass, rather than infiltrating within it (Bell et al, 1999;Tsuge et al, 2000). Further recent data from two collaborative laboratories, using different methods and samples, demonstrated that the activation of DC was very low or absent within the breast cancer microenvironment using a variety of markers (Coventry et al, 2002).…”

Water Extract of Cordyceps militaris Enhances Maturation of Murine Bone Marrow-Derived Dendritic Cells in Vitro

“…Nevertheless, from the analyses of tumor specimens obtained from patients, a reduced number of DC infiltrated into tumors correlates with a poor prognosis for patients. 26,27) Also, the phenotypes and function of DC could be altered in tumors. DC infiltrated into tumor tissue showed a reduced expression of co-stimulatory molecules, defective cytokine production, and full allostimulatory activity, implying that tumor-derived factors impede DC maturation.…”