Irradiated tumor cells of lipopolysaccharide stimulation elicit an enhanced anti-tumor immunity

J Cancer Res Clin Oncol. 2014 Nov;140(11):1815-23. doi: 10.1007/s00432-014-1721-4. Epub 2014 Jun 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / radiation effects
  • Cell Line, Tumor
  • Female
  • Hybridomas
  • Immunotherapy, Adoptive
  • Lipopolysaccharides / pharmacology*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy*
  • Mice, Inbred C57BL
  • Spleen / immunology
  • Tumor Burden / immunology
  • Vaccination
  • Xenograft Model Antitumor Assays

Substances

  • Cancer Vaccines
  • Lipopolysaccharides