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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Calcium-Binding Proteins, Carcinoma, Hepatocellular, Cell Line, Dendritic Cells, Disease Models, Animal, Disease Progression, Female, Humans, Immunotherapy, Leukocytes, Mononuclear, Liver Neoplasms, Membrane Proteins, Mice, Mice, Inbred BALB C, Mixed Function Oxygenases, Muscle Proteins, Neoplasm Invasiveness, Neoplasm Recurrence, Local.
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Is tumor progression-related transmembrane protein aspartate-β-hydroxylase a target for immunotherapy of hepatocellular carcinoma? Context: Hepatocellular carcinoma (HCC) has a poor survival rate due to recurrent intrahepatic metastases and lack of effective adjuvant therapy. Aspartate-β-hydroxylase (ASPH) is an attractive cellular target since it is a highly conserved transmembrane protein overexpressed in both murine and human HCC tumors, and promotes a malignant phenotype as characterized by enhanced tumor cell migration and invasion. Dendritic cells (DCs), expanded and isolated from the spleen, were incubated with a cytokine cocktail to optimize IL-12 secretion and co-stimulatory molecule expression, then subsequently loaded with ASPH protein for immunization. Mice were injected with syngeneic BNL HCC tumor cells followed by subcutaneous inoculation with 5-10×10(5) ASPH loaded DCs using a prophylactic and therapeutic experimental approach. Tumor infiltrating lymphocytes (TILs) were characterized, and their role in producing anti-tumor effects determined. The immunogenicity of ASPH protein with respect to activating antigen specific CD4+ T cells derived from human peripheral blood mononuclear cells (PBMCs) was also explored. We found that immunotherapy with ASPH-loaded DCs suppressed and delayed established HCC and tumor growth when administered prophylactically. Ex-vivo re-stimulation experiments and in vivo depletion studies demonstrated that both CD4+ and CD8+ cells contributed to anti-tumor effects. Using PBMCs derived from healthy volunteers and HCC patients, we showed that ASPH stimulation led to significant development of antigen-specific CD4+ T-cells.
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Immunization with ASPH-loaded DCs has substantial anti-tumor effects which could reduce the risk of HCC recurrence. Final Decision: yes