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 mlcroenviomment 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.