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Effect of Dendritic Cells Loaded with Tumor Antigens on Antitumor Activity of Tumor-Infiltrating Lymphocytes from Hepatocellular Carcinoma in vitro
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Abstract:
Objective:To investigate the effects of dendritic cells(DCs) loaded with tumor antigens on the proliferation and antitumor activity of tumor-infiltrating lymphocytes(TILs) from hepatocellular carcinoma (HCC) in vitro. Methods:DCs derived from the peripheral blood of patients with HCC were loaded with autologous tumor lysate(Tuly) to generate DC-Tuly and then the DC-Tuly was co-cultured with autologous TILs in low concentration of IL-2. TILs were counted, and the phenotypes of DCs and TILs were assayed by FCM and the cytotoxicity of TILs was determined with LDH method. The concentration of cytokines in TILs culture supernatant such as IFN-γ and TNF-α was detected by ELISA . Results:The expression levels of CD1a, CD80, CD83,CD86, CD40, HLA-DR molecules on the DC-Tuly are notably increased（P<005）. The proliferation of TILs which were induced by DC-Tuly was markedly enhanced (P<0.01) and the cytotoxicity of the TILs against autologous tumor cells was remarkably increased (P<0.01). After co-cultured with DC-Tuly, CD3+TILs were increased（P<0.05）and the percentage of CD4+ TILs was enhanced(P<0.01), however, the percentage of CD8+ TILs was still higher than that of CD4+ TILs. Both concentrations of IFN-γ and TNF-α in the culture supernatant of the TILs distinctly increased on the 1st and 2nd days of co-culturing (P<0.01). Conclusion: DCs loaded with tumor antigens can obviously promote the proliferation and the specific antitumor activity of TILs.
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