Interleukin-12-anchored exosomes increase cytotoxicity of T lymphocytes by reversing the JAK/STAT pathway impaired by tumor-derived exosomes

  • Authors:
    • Yao Zhang
    • Xiao-Hou Wu
    • Chun-Li Luo
    • Jia-Mo Zhang
    • Bai-Cheng He
    • Gang Chen
  • View Affiliations

  • Published online on: May 1, 2010     https://doi.org/10.3892/ijmm_00000393
  • Pages: 695-700
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Abstract

Tumor-derived exosomes express tumor antigens, leading to their promising utility as tumor vaccines, but they also can suppress T-cell signaling molecules and reduce cytotoxic effects. We investigated whether interleukin-12 (IL-12)-anchored exosomes (EXO/IL-12) reverse tumor exosome-mediated inhibition of T-cell activation and cytotoxicity was associated with inhibition of JAK3 and p-STAT5. A co-expression plasmid of pBudCE4.1/IL-12A/ IL-12B-GPI was constructed. EXO/IL-12 was identified by transmission electron microscopy and Western blotting, which induced proliferation and cytotoxicity of T-cells and were analyzed by CFSE-based flow cytometry. Expression of JAK2, JAK3 and p-STAT5 was detected by Western blotting. Our results showed that EXO/IL-12 was much more efficient in induction of the proliferation, release of IFN-γ and cytotoxic effect of T lymphocytes than conventional exosomes in vitro. Exosomes inhibited the expression of JAK3 and phosphorylation of STAT5 in high doses in T-cells, but not JAK2, while EXO/IL-12 had much less attenuated reduction of the expression of p-STAT5. The enhanced cytotoxic effects of T lymphocytes might partly depend on EXO/IL-12 reversing the suppressed expression of p-Stat5 by Jak2/Stat5 pathway. These findings might provide an alternative approach for developing exosomes into tumor vaccines.

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May 2010
Volume 25 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhang Y, Wu X, Luo C, Zhang J, He B and Chen G: Interleukin-12-anchored exosomes increase cytotoxicity of T lymphocytes by reversing the JAK/STAT pathway impaired by tumor-derived exosomes. Int J Mol Med 25: 695-700, 2010.
APA
Zhang, Y., Wu, X., Luo, C., Zhang, J., He, B., & Chen, G. (2010). Interleukin-12-anchored exosomes increase cytotoxicity of T lymphocytes by reversing the JAK/STAT pathway impaired by tumor-derived exosomes. International Journal of Molecular Medicine, 25, 695-700. https://doi.org/10.3892/ijmm_00000393
MLA
Zhang, Y., Wu, X., Luo, C., Zhang, J., He, B., Chen, G."Interleukin-12-anchored exosomes increase cytotoxicity of T lymphocytes by reversing the JAK/STAT pathway impaired by tumor-derived exosomes". International Journal of Molecular Medicine 25.5 (2010): 695-700.
Chicago
Zhang, Y., Wu, X., Luo, C., Zhang, J., He, B., Chen, G."Interleukin-12-anchored exosomes increase cytotoxicity of T lymphocytes by reversing the JAK/STAT pathway impaired by tumor-derived exosomes". International Journal of Molecular Medicine 25, no. 5 (2010): 695-700. https://doi.org/10.3892/ijmm_00000393