BACKGROUND: We investigated whether GM-CSF/IL-4 is the most efficient cytokine combination for differentiating dendritic cells (DC) in terms of its ability to elicit an antitumor immune response. MATERIALS AND METHODS: Two experimental models were examined: C57BL/6 mice bearing MC38 cells and Balb/c mice bearing cachexia-inducible Colon-26 cells. After immunization with DC pulsed with whole tumor cell lysate, tumors were inoculated into the subcutis. RESULTS: C57BL/6 mice immunized with lysate-pulsed DC effectively rejected the MC38 challenge and detectable MC38-specific cytotoxic lymphocytes (CTL) were observed. However, even those groups immunized with lysate-pulsed DC exhibited no protective immunity against Colon-26 challenge in Balb/c mice. Unexpectedly, mice inoculated with lysate-unpulsed DC showed an acceleration of cachectic progression (p=0.031) compared to control mice. CONCLUSION: We speculate that GM-CSF/IL-4-induced DC promotes Th2-dominated immunity in Balb/c mice. Consideration might be given to which combination of cytokines is appropriate for the ex vivo differentiation of DC in tumor immunotherapy.
BACKGROUND: We investigated whether GM-CSF/IL-4 is the most efficient cytokine combination for differentiating dendritic cells (DC) in terms of its ability to elicit an antitumor immune response. MATERIALS AND METHODS: Two experimental models were examined: C57BL/6 mice bearing MC38 cells and Balb/c mice bearing cachexia-inducible Colon-26 cells. After immunization with DC pulsed with whole tumor cell lysate, tumors were inoculated into the subcutis. RESULTS: C57BL/6 mice immunized with lysate-pulsed DC effectively rejected the MC38 challenge and detectable MC38-specific cytotoxic lymphocytes (CTL) were observed. However, even those groups immunized with lysate-pulsed DC exhibited no protective immunity against Colon-26 challenge in Balb/c mice. Unexpectedly, mice inoculated with lysate-unpulsed DC showed an acceleration of cachectic progression (p=0.031) compared to control mice. CONCLUSION: We speculate that GM-CSF/IL-4-induced DC promotes Th2-dominated immunity in Balb/c mice. Consideration might be given to which combination of cytokines is appropriate for the ex vivo differentiation of DC in tumor immunotherapy.
Authors: Melissa Hunter; Yijie Wang; Tim Eubank; Christopher Baran; Patrick Nana-Sinkam; Clay Marsh Journal: Front Biosci (Landmark Ed) Date: 2009-01-01