Big Tumor Regression Induced by 3LL‐GM Inoculation via Facilitating DC Maturation and Deviation towards CD11c+CD8alpha+ Subset

Abstract

GM‐CSF is a powerful immune stimulating factor to help to generate a systemic, strong and long‐lasting immune response. To determine whether the transduction of GM‐CSF to tumor cell could result in the big tumor regression and optimize local immune micro‐environment, in this study, using an experimental murine NSCLC tumor model, we demonstrated that the in vivo growth of 3LL tumor cells harboring GM‐CSF gene (3LL‐GM) was inhibited even when the tumor diameter was over 7mm (big tumor), and mice inoculated with 3LL‐GM survived over 90 days, whereas mice inoculated with control parental 3LL cells and 3LL cells transduced with control vector all succumbed to the tumor by day 17 after tumor inoculation. Further analysis showed that targeted expression of GM‐CSF in 3LL tumor cells markedly enhanced the systemic anti‐tumor effect including the specific lymphocytes proliferation, cytotoxicity against 3LL tumor as well as the higher production of IFN‐gamma. 3LL‐GM tumor significantly protected the mice from the parental 3LL tumor challenge. More importantly, the percentage of DC in tumor site was greatly increased and the differentiation of DC altered to CD11c+CD8alpha+ subsets, which benefits the induction of CD8+ CTL and consequently kills the tumor. Our research indicated that GM‐CSF could optimize the immune micro‐environment in tumor site and result in the big tumor regression, which provides a potent approach for immunotherapy of cancer.