It has been well established that immune surveillance plays critical roles in preventing the occurrence and prog-ression of tumor.More and more evidence in recent years showed the host anti-tumor immune responses also...It has been well established that immune surveillance plays critical roles in preventing the occurrence and prog-ression 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 microenvir-onment in combination with other therapeutic strategies.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.91029719)the National Key Basic Research Program of China(No.2012CB917101).
文摘It has been well established that immune surveillance plays critical roles in preventing the occurrence and prog-ression 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 microenvir-onment in combination with other therapeutic strategies.
