Volume 3 Issue 6
Jun.  2012
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Meng Xu, Xuexiang Du, Mingyue Liu, Sirui Li, Xiaozhu Li, Yang-Xin Fu, Shengdian Wang. The tumor immunosuppressive microenvironment impairs the therapy of anti-HER2/neu antibody[J]. Protein&Cell, 2012, 3(6): 441-449. doi: 10.1007/s13238-012-2044-3
Citation: Meng Xu, Xuexiang Du, Mingyue Liu, Sirui Li, Xiaozhu Li, Yang-Xin Fu, Shengdian Wang. The tumor immunosuppressive microenvironment impairs the therapy of anti-HER2/neu antibody[J]. Protein&Cell, 2012, 3(6): 441-449. doi: 10.1007/s13238-012-2044-3

The tumor immunosuppressive microenvironment impairs the therapy of anti-HER2/neu antibody

doi: 10.1007/s13238-012-2044-3
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This work was supported by grants from the National Natural Science Foundation of China (Grant No. 91029719) and the National Key Basic Research Program of China (No. 2012CB917101).

  • Received Date: 2012-05-08
  • Rev Recd Date: 2012-05-21
  • It has been well established that immune surveillance plays critical roles in preventing the occurrence and progression of tumor. More and more evidence in recent years showed the host anti-tumor immune responses also play important roles in the chemotherapy and radiotherapy of cancers. Our previous study found that tumor-targeting therapy of anti-HER2/neu mAb is mediated by CD8+ T cell responses. However, we found here that enhancement of CD8+ T cell responses by combination therapy with IL-15R/IL-15 fusion protein or anti-CD40, which are strong stimultors for T cell responses, failed to promote the tumor therapeutic effects of anti-HER2/neu mAb. Analysis of tumor microenviornment showed that tumor tissues were heavily infiltrated with the immunosuppressive macrophages and most tumor infiltrating T cells, especially CD8+ T cells, expressed high level of inhibitory co-signaling receptor PD-1. These data suggest that tumor microenvironment is dominated by the immunosuppressive strategies, which thwart anti-tumor immune responses. Therefore, the successful tumor therapy should be the removal of inhibitory signals in the tumor microenvironment in combination with other therapeutic strategies.
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