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

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• 作者：Meng Xu (1) (2)
  Xuexiang Du (1) (2)
  Mingyue Liu (1) (2)
  Sirui Li (1) (2)
  Xiaozhu Li (1)
  Yang-Xin Fu (1) (3)
  Shengdian Wang (1)
  
• 关键词：anti ; HER2/neu antibody ; CD8+ T cells ; tumor microenvironment ; tumor therapy ; immune suppression
• 刊名：Protein & Cell
• 出版年：2012
• 出版时间：June 2012
• 年：2012
• 卷：3
• 期：6
• 页码：441-449
• 全文大小：623KB
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• 作者单位：Meng Xu (1) (2)
  Xuexiang Du (1) (2)
  Mingyue Liu (1) (2)
  Sirui Li (1) (2)
  Xiaozhu Li (1)
  Yang-Xin Fu (1) (3)
  Shengdian Wang (1)
  
  1. Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
  2. Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, 100049, China
  3. Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL, 60637, USA
  

文摘

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.