Prognostic value of tumor-infiltrating dendritic cells expressing CD83 in human breast carcinomas.

DCs are the most potent antigen-presenting cells that play a major role in initiating the antitumor immune response. Although the clinical significance of TIDCs has been investigated in a variety of human cancers, few studies have focused on the in situ maturation status of DCs. We have analyzed the maturation-specific significance of TIDCs in the prognosis of patients with breast carcinoma. We evaluated 130 breast carcinomas for the presence of TIDCs using immunohistochemistry with an anti-CD1a antibody for immature DCs and an anti-CD83 antibody for mature DCs. Intratumoral expression of immunosuppressive cytokines was also examined. All samples contained CD1a(+) TIDCs, and 82 (63.1%) samples contained CD83(+) TIDCs. The number of CD83(+) TIDCs was inversely correlated with lymph node metastasis and with tissue expression of VEGF and TGF-beta, whereas the number of CD1a(+) TIDCs was not. Kaplan-Meier analysis (log rank statistics) revealed a significant association of increasing number of CD83(+) TIDCs with longer relapse-free (p = 0.002) and overall (p < 0.001) survival. Furthermore, among patients with lymph node metastasis, the survival rate of those with larger numbers of CD83(+) TIDCs was significantly better than that of patients with fewer CD83(+) TIDCs. Multivariate analysis revealed that CD83(+) TIDCs had independent prognostic relevance in breast carcinomas. The infiltration of tumors by mature DCs expressing CD83 may be of great importance in initiating the primary antitumor immune response and is confirmed as an independent, immunologic prognostic parameter for survival in patients with breast cancer.

Clinical study to identify specific characteristics of cancer newly developed in the remnant stomach.

BACKGROUND: Cancer newly developed in the remnant stomach (CRS) after partial gastrectomy is worthy of attention not only because it is a typical model of carcinogenesis but also from the aspect of cancer diagnosis. METHODS: We treated 47 patients with CRS in the 20 years from 1979 to 1998. Clinicopathological variables, as well as long-term survival results after the second surgery, were reviewed to clarify whether there were any differences in the characteristics of this disease entity compared with the usual primary gastric cancer. RESULTS: The mean time interval between the initial surgery and surgery for CRS was 25.8 years for patients with CRS with previous benign gastric lesions, and 10.6 years for those with previous gastric cancer. CRS was frequently detected at an early stage in the patients with previous cancer, and in the patients who had undergone reconstruction by the Billroth I method (regardless of the primary nature of the disease). Cancers with a differentiated histology developed more frequently in the patients who had undergone the initial surgery for cancer disease. Long-term survival results after the second surgery clearly demonstrated that surgical treatment for CRS was as effective as that for primary cancer in the upper stomach (PUC). In addition, it was confirmed that new lymphatic drainage into the lower mediastinum or the jejunal mesentery had developed after the initial gastric surgery. CONCLUSION: The findings suggested that patients with CRS and those with PUC should be treated similarly, although the findings of a high incidence of lymph node metastasis to the lower mediastinum and/or to the jejunal mesentery in the CRS patients should be taken into consideration.

PSK, a protein-bound polysaccharide, overcomes defective maturation of dendritic cells exposed to tumor-derived factors in vitro.

Dendritic cells (DC) are the most potent antigen-presenting cells that induce specific anti-tumor immunity. To obtain potent efficacy of immunotherapy using infusion of activated DC, it is necessary to overcome defective function of DC in tumor-bearing patients. We examined whether the treatment with PSK, a biological response modifier derived from Basidiomycetes, could allow DC to avoid inhibition of functional maturation by tumor-derived factors in vitro. CD14+ monocyte-derived DC were generated by stimulating with granulocyte-macrophage colony-stimulating factor and interleukin (IL)-4 in the presence or absence of PSK (100 microg/ml), by exposure to a tumor culture supernatant (TSN) of MKN-45P human gastric cancer cells. TSN-exposed DC were not effective in inducing cytotoxic T lymphocyte-mediated growth inhibition of target HT29 human colon cancer cells. In contrast, the presence of PSK significantly resuscitated the defective cytotoxicity. This beneficial outcome was accompanied by an increase in phagocytic activity as measured by fluorescein isothiocyanate-conjugated dextran, expression of CD83 (maturation-specific phenotype), overexpression of a CD86 co-stimulatory molecule, preserved production of IL-12 that plays a key role in the induction of Th1-type immune regulations, and protection against TSN-induced apoptosis of DC. These results demonstrated that PSK overcomes defective maturation of DC exposed to tumor-derived factors in vitro, and suggest the efficacy of PSK in DC-based immunotherapy in cancer patients.