IntroductionTumorigenesis is associated with a wide array of both genetic and epigenetic changes that give rise to tumor-associated antigens capable of eliciting a host antitumor immune response. Although host immune surveillance may prevent tumor outgrowth during the earliest stages of tumor growth, locally invasive or metastatic tumors must evade host immunity. 1 Immune escape is not merely a passive process of immune evasion but an active one by which both tumor cells and stromal cells present within the tumor microenvironment actively suppress the antitumor immune response. This distinction between immune evasion and suppression is an important one and may explain the paradoxical observation that many tumor immunotherapy clinical trials, despite eliciting an antitumor immune response, are not associated with a meaningful clinical response. 2 Improved mechanistic understanding of tumor-associated immune suppression is needed if the next generation of immunotherapeutic strategies is to be rationally designed.Malignant cells may suppress host immunity directly, by producing immunoregulatory cytokines or expressing inhibitory ligands on their cell surface. In addition, malignant cells may influence the tumor microenvironment leading to the induction or recruitment of immunoregulatory cells capable of suppressing host immunity. 3 Both myeloid-derived cells (including tumor-associated macrophages, dendritic cells [DCs], and myeloid-derived suppressor cells) and lymphocyte subsets, most notably regulatory T (Treg) cells, present within the tumor microenvironment, collaborate with their malignant counterparts to suppress host immunity. 3,4 The microenvironment's role in promoting tumor growth in nonHodgkin lymphoma (NHL) was recently highlighted by both gene expression profiling and immunohistochemistry-based approaches. [5][6][7] Therapeutic approaches capable of targeting the tumor microenvironment are currently being translated into clinical practice in hematologic malignancies and may be associated with improved outcomes. 8,9 Fundamentally, 2 distinct approaches capable of targeting the tumor microenvironment may be imagined. The first seeks to eliminate immunosuppressive cells present within the tumor microenvironment and is highlighted by recent attempts to eliminate Treg. As different stromal cells may use common immunosuppressive mediators, the alternative approach seeks to identify and neutralize these shared molecular mediators of host immune suppression.Members of the B7 family have emerged as important mediators of host immune suppression. In contrast to B7-1 (CD80) and B7-2 (CD86), which play an important role in T-cell activation and costimulation, the B7 homologs (B7-H, including B7-H1, B7-H2, B7-H3, and B7-H4), which have been described more recently may function as important "coinhibitors" of host T-cell immunity and have been associated with poor clinical outcomes in a variety of human tumors. 10,11 B7-H1, for example, may be inducibly expressed on tumor cells and confer resistance to killing media...