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Since the discovery of dendritic cells (DCs) by Ralph Steinman and Zanvil Cohn 40 years ago (1), the role of these cells as critical regulators of immune tolerance versus activation has emerged as one of the most fundamental concepts in the field of immunology. Serving as a link between the innate and adaptive immune systems, DCs exhibit sensitive immune surveillance capabilities that enable their acquisition of antigens from a variety of sources in peripheral tissues, and they possess unique sensory properties and antigen processing machinery that enable their transformation into potent antigen-presenting cells (APCs). Importantly, the outcome (immune tolerance versus activation) of antigen presentation to T cells by DC is dependent on the maturation and activation state of the DC, and significant efforts over the last 20+ years have therefore focused on understanding factors that regulate DC maturation and activation. While their role in self-tolerance and the activation of T cell immunity to foreign pathogens has long been appreciated, more recently DCs have also been shown to play important roles in the regulation of anti-tumor immune responses. Since this time, considerable efforts have been placed on understanding many facets of tumor-associated DC, including: the induction, regulation, and maintenance of anti-tumor immunity by DC; tumor-associated interference with these processes to subvert anti-tumor immunity; and the application of this knowledge to develop therapeutic strategies for improving DC-mediated anti-tumor immune responses. In this collection of articles, we highlight our current understanding of the role played by DC in anti-tumor immunity and focus attention on important questions that remain to be answered in the field as we aim to improve the immunogenicity of tumor-associated DC and the outcome of DC-mediated anti-tumor immune responses in the future.

The Role of Tumor/Dendritic Cell Interactions in the Regulation of Anti-Tumor Immunity: The Good, the Bad, and the Ugly