Potentiation of the immunotherapeutic effect of autologous dendritic cells by pretreating hepatocellular carcinoma with low-dose radiation

Abstract

Purpose: To determine whether exposing hepatocellular carcinoma (HCC) to low dose radiation increases the efficacy of dendritic cell-mediated immunotherapy for HCC.

Methods: Tumour specimens collected from 20 recruited patients with HCC were cultured in primary culture (half successfully) and then exposed to low-dose radiation (0.5 Gy). Immature DCs derived from peripheral blood monocytes of patients were pulsed with autologous HCC cell lysates and matured with a cytokine cocktail. Autologous tumour lysate-pulsed DCs (TLP-DCs) were used to stimulate mixed lymphocytes, which were then tested for inhibitory effect on the growth of HCC cells. Surface markers of immunogenicity on primary HCC cells, MHC, and Fas were investigated before and after low-dose irradiation.

Results: Exposing HCC cells to low-dose (0.5 Gy) radiation enhanced the immunotherapeutic effect of TLP-DC-stimulated lymphocytes. Growth inhibition increased from 50.6+/-7.5% without irradiation to 74.3+/-4.3% with radiation. The expression of MHC class ll and Fas was upregulated after irradiating HCC cells.

Conclusion: Exposing tumour cells to a low dose of radiation can enhance the immunotherapeutic effect of the autologous tumor lysate-pulsed DC vaccine.