A study on enhanced anti-tumor immunity induced by high level expression of GM-CSF in 3LL tumor site of the mice

Background and purpose:Grannulocyte/monocyte-colony stimulating factor(GM-CSF)can facilitate maturation of immature dendritic cells(DC),upregulate their MHC molecules and co-stimulating factors,as well as enhance tumor antigen presentation by DC.Our study was to investigate whether high level expression of GM-CSF in tumor site could induce enhanced anti-tumor immune response and its mechanism.Methods:3LL-GM was established by transduction of 3LL,Lewis lung cancer cell line,with lentivirus coded with GM-CSF gene.C57BL/6 mice were inoculated subcutaneously with 3LL,3LL-vec and 3LL-GM,respectively.DC maturation and the percentage of DC subsets,as well as the activation and function of lymphocytes especially CD8+ effector T lymphocytes in tumor site were detected.Results:The concentration of GM-CSF in 3LL-GM tumor sites was 441.22 ng/g tumor,significantly higher than in parental 3LL tumor site(0.53 ng/g tumor,P0.05)and in vector control 3LL-vec tumor site(0.42 ng/g tumor,P0.05).In 3LL-GM group,3LL and 3LL-vec group,percentages of I-Ab+ cells in tumor infiltrating CD11c+ DCs were 60.62%,19.98% and 23.12% respectively(P0.05),and percentages of CD80+ cells were 60.93%,37.43% and 47.03% respectively(P0.05),indicating that GM-CSF in a tumor site can facilitate maturation of DCs.Meanwhile,proportions of tumor infiltrating CD11c+CD8α+CD4-DC in 3 groups were 60.82%,40.00% and 29.27% respectively(P0.05),showing elevated differentiation into CD11c+CD8α+CD4-DC subset induced by local GM-CSF.Moreover,CD3+CD62Llow cells in tumor infiltrating lymphocytes(TILs)of 3LL-GM group was 20.84%,significantly higher than those of 3LL group(6.34%,P0.05)and 3LL-vec group(15.18%,P0.05).More importantly,percentage of IFN-secreting CD8+ T lymphocytes was 2.77%,showing significant statistical difference from the control group(P0.05),and consequently caused marked tumor regression.Conclusions:GM-CSF that was highly expressed in tumor site and could induce enhanced anti-tumor immune response by upregulating DC maturation and biasing DC subset to the CD11c+CD8α+CD4-DC in tumor site.