[Two case reports on intra-tumor injection therapy of dendritic cells].

DC (dendritic cells) vaccine therapy against cancer has attracted attention in recent years. However, the existence of the immunosuppressive state in cancer individuals leads to anergy and failure in cytotoxic T cell (CTL) induction and DC migration to the target organ. It has been reported that injected intra-tumor DC is expected to work phagocytosis of the tumor as a localized effect, the consequent CTL induction in the tumor and the regional lymphnodes, resulting in a systemic effect. Two cases reported in this article were performed with intra-tumor DC injection therapy by means of EUS (endoscopic ultrasonography) which indicated interesting immunoreaction.

Effects of PSK on T and dendritic cells differentiation in gastric or colorectal cancer patients.

BACKGROUND: Vaccine therapy targeting tumor antigens recognized by cytotoxic T cells (CTL) has been tried extensively. However, in a cancer-bearing state, the Th1/Th2 balance shifts to Th2 dominance, and this has been the obstacle to vaccine therapy to induce the CTL. DC1/DC2 subsets have also been reported to control the differentiation of Th subsets. The key to tumor immunotherapy is how to activate the DC1-Th1 lineage. PATIENTS AND METHODS: Six normal adults and 14 patients with gastric or colorectal cancers, who gave informed consent, were studied. The Th1/Th2 and DC1/DC2 ratios were determined by FACS. IL-12 and IL-10 production from PBMC were measured by ELISA. RESULTS: The Th1/Th2 and DC1/DC2 ratios were all significantly lower in the patients with gastric or colorectal cancers compared to normal adults. After protein-bound polysaccharide K (PSK) therapy in cancer patients, the Th1/Th2 balance shifted to Th1 dominance and the DC1/DC2 balance to DC1 dominance. IL-10 production was significantly decreased by PSK therapy. CONCLUSION: In the cancer-bearing state, the Th1/Th2 and DC/1/DC2 balance becomes Th2- and DC2-dominant. PSK therapy results in a shift of the Th1/Th2 and DC1/DC2 balance towards Th1 and DC1 dominance. We plan to examine whether combining dendritic cells (DC) vaccination therapy with oral PSK enhances the induction of T cell and DC differentiation in cancer patients.

[Case report on intra-tumor injection therapy of dendritic cells in advanced gastric cancer].

Dendritic cells (DC) are powerful antigen-presenting cells, and have attracted attention in recent years from the viewpoint of DC vaccine therapy against cancer. However, the existence of an immunosuppressive state in cancer individuals leads to anergy and failure in cytotoxic T cell (CTL) induction and DC migration to the target organ. It has been reported that injected intra-tumor DCs are expected to work phagocytosis of the tumor as a localized effect. Consequently CTL induction in the tumor and the regional lymphnodes results in a systemic effect. In this study, intra-tumor DC injection therapy was performed by means of endoscopic ultrasonography (EUS) in 2 gastric cancer cases. As a result, tumor markers and ascites of one case were on the decrease. The results indicate this method can be useful in advanced cancer patients.

Effect of PSK on the maturation of dendritic cells derived from human peripheral blood monocytes.

Dendritic cells (DCs) are powerful antigen-presenting cells (APCs) that have attracted attention in recent years from the viewpoint of DC vaccine therapy against cancer. However, the existence of a strongly immunosuppressed state in cancer-bearing individuals inhibits DC maturation, which is one of the problems facing anti-cancer DC vaccine therapy. Protein-bound polysaccharide K (PSK), which is extracted from the cultured mycelium of Coriolus versicolor (Fr.) Quél, is used as an anti-cancer agent in Japan. PSK is reported to improve the immunosuppressed state and might be associated with DC maturation directly. We examined the effect of PSK on the maturation of DC derived from CD14-positive cells obtained from human peripheral blood monocytes using a negative selection method. CD14-positive cells cultured in the presence of PSK significantly increased the expression of HLA class II antigen and CD40; significantly increased the number and expression of CD80-, CD86- and CD83-positive cells; decreased Fluorescein isothiocyanate (FITC)-dextran uptake, augmented IL-12 production; augmented the allogeneic mixed lymphocyte reaction; and induced antigen-specific cytotoxicity. These results indicate that PSK promotes both the phenotypic and functional maturation of DC derived from human CD14-positive mononuclear cells. The clinical significance of the combined use of PSK in DC vaccine therapy remains for study.

[Effect of DC therapy combined with chemotherapy in advanced cancer cases].

Dendritic cells (DC) are powerful antigen-presenting cells, and have attracted attention in recent years from the viewpoint of DC vaccine therapy against cancer. However, the existence of an immunosuppressive state in cancer individuals leads to anergy and immunotolerance, which has been reported to be caused by T cell and DC immunosuppressive subsets or cytokines such as Th2, Tc2, CD4+CD25+, DC2 and IL-10 against Th1, Tc1, DC1 and IL-12. Therefore, DC therapy could be incompatible with severe chemotherapy. Conversely, there are some reports that indicate tumor specific cytotoxicity in DC therapy could be augmentedly un exposure to tumor antigen caused by apoptosis in combination radiation or chemotherapy. In this study we examined the usefulness of DC therapy combined with chemotherapy and BRM (PSK) administration by analyzing the immunocyte subsets and cytokines as well as the combination effect. The results indicate this method can be useful in advanced cancer patients.