Specific anti-tumor immune responses of dendritic cells pulsed with recombinant human rhHSP70 and freeze-thaw cellular lysates derived from breast cancer / 中国肿瘤临床

ABSTRACT

Objective:This work aims to use the characteristics of dendritic cells (DCs) pulsed with recombinant human HSP70, which can present and process tumor antigens, to enhance the killing activity of cytotoxic t lymphocytes (CTLs) against breast neoplasms. Methods:Autologous DCs were isolated from peripheral blood mononuclear cells and then stimulated in vitro with granulocyte macrophage-colony stimulating factor and interleukin-4. The DCs were loaded with A549 tumor cell freeze-thaw lysate, and rhHSP70 was added as an immune adjuvant. The specific groups were subjected to tumor-specific cytotoxic assay, enzyme-linked immunosorbent assay, and fluores-cence-activated cell sorting. Results:DCs pulsed with A549 tumor cell lysate enhanced the growth expansion of CTLs, upregulated CD40 and CD80 populations in CTLs, and augmented Th1 cytokines. In addition, the cytotoxicity of specific CTLs against A549 was highly enhanced. The above indications became more obvious after the addition of rhHSP70. Conclusion:DCs pulsed with freeze-thaw cell lysates derived from breast cancer can enhance growth expansion of lymphocytes. They may serve as an effective tumor antigen to stimulate the proliferation of specific CTLs, which are very effective in activating specific T-cell responses against breast cancer cells in vitro. The improved anti-tumor immunity response by DC-based vaccines may be related to the maturation of the DCs promoted by rhHSP70.