Optimized generation of survivin-specific cytotoxic T lymphocytes against lung cancer

Abstract

Cancer immunotherapy based on dendritic cells (DCs) that target survivin is a promising strategy with potential clinical applications. However, the translation of survivin-specific cytotoxic T-lymphocyte (CTL) immunotherapy into the clinical setting has numerous challenges, including the low efficiency of the treatment. The present study aimed to improve the efficiency of the treatment, and found that treatment with interleukin 4 (IL-4)/granulocyte macrophage colony-stimulating factor (GM-CSF) and a combination of proinflammatory cytokines significantly increased the antigen-presenting and -capture abilities of DCs that expressed exogenous survivin. Furthermore, lipopolysaccharide (LPS) stimulation enhanced the DC response to subsequent T-cell signals and the extent of T-cell activation. In addition, the efficiency of surviving-specific CTLs was examined, and high cytotoxicity against surviving-expressing A549 lung cancer cells was observed. However, the cytotoxicity of CTLs was significantly reduced in A549 cells with silenced survivin expression. The present study provides a novel method to optimize the generation of surviving-specific CTLs against lung cancer cells, which may advance the translation of surviving-specific CTL immunotherapy into clinical use for the treatment of cancer.