Yuli Li1, Guobo Shen, Wen Nie, Zhimian Li, Yaxiong Sang, Binglan Zhang, Yuquan Wei. 1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Gaopeng Street, Keyuan Road 4, Chengdu, 610041, Sichuan, People's Republic of China.
Abstract
PURPOSE: Lipopolysaccharide (LPS) is a major component of the outer surface membrane of Gram-negative bacteria which has been proved an effective immune enhancer. Here, we investigated the anti-tumor effect of irradiated tumor cells that stimulated by LPS in mouse xenografts models. METHODS: Tumor cells were irradiated after stimulation with 1 μg/mL LPS for 48 h. The C57BL/6 mice were immunized subcutaneously with irradiated tumor cells. The anti-tumor effect of lymphocytes of immunized mice was investigated. The cytotoxicity of spleen lymphocytes from immunized mice was determined by a standard (51)Cr-release assay. The roles of immune cell subsets in anti-tumor activity were assessed by injected intraperitoneally with monoclonal antibodies. RESULTS: We observed that the vaccine of irradiated tumor cell with LPS-stimulated elicited a stronger protective anti-tumor immunity than other controls. Adoptive transfer of lymphocytes of immunized mice showed that the cellular immune response was involved in the anti-tumor effect. And this effect was achieved by activation of antigen-specific CD8(+) T cell response and reduction of myeloid-derived suppressor cells (MDSCs, Gr1(+) CD11b (+) ), which were confirmed by depletion of immune cell subsets and flow cytometry analysis. CONCLUSIONS: In summary, our study showed that stimulation of LPS was able to enhance anti-tumor immunity of vaccination with tumor cells after irradiation treatment, which might be a new strategy for cancer therapy.
PURPOSE:Lipopolysaccharide (LPS) is a major component of the outer surface membrane of Gram-negative bacteria which has been proved an effective immune enhancer. Here, we investigated the anti-tumor effect of irradiated tumor cells that stimulated by LPS in mouse xenografts models. METHODS:Tumor cells were irradiated after stimulation with 1 μg/mL LPS for 48 h. The C57BL/6 mice were immunized subcutaneously with irradiated tumor cells. The anti-tumor effect of lymphocytes of immunized mice was investigated. The cytotoxicity of spleen lymphocytes from immunized mice was determined by a standard (51)Cr-release assay. The roles of immune cell subsets in anti-tumor activity were assessed by injected intraperitoneally with monoclonal antibodies. RESULTS: We observed that the vaccine of irradiated tumor cell with LPS-stimulated elicited a stronger protective anti-tumor immunity than other controls. Adoptive transfer of lymphocytes of immunized mice showed that the cellular immune response was involved in the anti-tumor effect. And this effect was achieved by activation of antigen-specific CD8(+) T cell response and reduction of myeloid-derived suppressor cells (MDSCs, Gr1(+) CD11b (+) ), which were confirmed by depletion of immune cell subsets and flow cytometry analysis. CONCLUSIONS: In summary, our study showed that stimulation of LPS was able to enhance anti-tumor immunity of vaccination with tumor cells after irradiation treatment, which might be a new strategy for cancer therapy.
Authors: Martin K Hunn; Kathryn J Farrand; Kate W R Broadley; Robert Weinkove; Peter Ferguson; Rose J Miller; Cameron S Field; Troels Petersen; Melanie J McConnell; Ian F Hermans Journal: Clin Cancer Res Date: 2012-11-12 Impact factor: 12.531
Authors: H M Horton; D Anderson; P Hernandez; K M Barnhart; J A Norman; S E Parker Journal: Proc Natl Acad Sci U S A Date: 1999-02-16 Impact factor: 11.205
Authors: Eric A Reits; James W Hodge; Carla A Herberts; Tom A Groothuis; Mala Chakraborty; Elizabeth K Wansley; Kevin Camphausen; Rosalie M Luiten; Arnold H de Ru; Joost Neijssen; Alexander Griekspoor; Elly Mesman; Frank A Verreck; Hergen Spits; Jeffrey Schlom; Peter van Veelen; Jacques J Neefjes Journal: J Exp Med Date: 2006-04-24 Impact factor: 14.307