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The interplay between tumors and their immunologic microenvironment is complex and difficult to decipher, but its understanding is of seminal importance for the development of novel prognostic markers and therapeutic strategies. This chapter discusses tumor−immune interactions in several human cancers that illustrate various aspects of this complexity and proposes an integrated scheme of the impact...
Tumor immune surveillance and CD8+ T cells in particular appear capable of recognizing the antigenic properties of human tumor cells. However, those antigen specific T cells are often excluded from tumor tissue or are functionally limited in their cytotoxic capacity. Instead, the immune response provides proinflammatory cytokines and proteases promoting tumor growth and progression while subverting...
Signal transducer and activator of transcription 3 (Stat3) has emerged as a critical regulator for tumor-associated inflammation. Activation of Stat3 negatively regulates the Th1-type immune response and promotes expansion of myeloid-derived suppressor cells (MDSCs) and regulatory T-cell functions in the tumor microenvironment. Mounting evidence suggests that Stat3 and related pathways may serve as...
This review specifically examines the role of regulatory T cells (Tregs) in cancer in both mice and the clinic. Due to the rapid refinement of the definition of Tregs and their heterogeneity, emphasis is given to research findings over the past three years. For clarity, this review is broadly divided into three short sections that outline the basic biology of Tregs – (1) Treg lineage and development,...
In this chapter, a detailed description of how the innate and adaptive immune responses interact with malignant cells is presented. In addition, we discuss how developing tumors establish themselves, and how they benefit on one hand and organize their defense against the immune system on the other hand. New data from three tumor model systems in mice are discussed; in particular, the intricate interactions...
Cancer immunotherapies have yielded promising results in recent years, but new approaches must be utilized if more patients are to experience the benefits of these therapies. Angiogenesis and the tumor endothelium confer unique immune privilege to a growing tumor, with significant effects on diverse immunological processes such as hematopoietic cell maturation, antigen presentation, effector T cell...
Cell-based therapies with various lymphocytes and antigen-presenting cells are promising approaches for cancer immunotherapy. The transfusion of T lymphocytes, also called adoptive cell therapy (ACT), is an effective treatment for viral infections, has induced regression of cancer in early stage clinical trials, and may be a particularly important and efficacious modality in the period following hematopoietic...
Current active immunotherapy trials have shown durable tumor regressions in a fraction of patients. However, the clinical efficacy of current vaccines is limited, possibly because tumors skew the immune system by means of myeloid-derived suppressor cells, inflammatory Type 2 T cells and regulatory T cells (Tregs), all of which prevent the generation of effector cells. To improve the clinical efficacy...
Idiotype protein, among the first identified tumor-specific antigens, has been found to stimulate both humoral and cellular responses in lymphoma and myeloma patients. With the increasing use of B cell depletion treatments such as rituximab in clinic, the cellular response mediated by idiotype-specific T cells has become increasingly important as an adjunct therapy for lymphoma and myeloma. Here,...
The rational manipulation of antigen-specific T cells to reignite a tumor-specific immune response in cancer patients is a challenge for cancer immunotherapy. Targeting coinhibitory and costimulatory T cell receptors with specific antibodies in cancer patients is an emerging approach to T cell manipulation, namely “immune modulation.” Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and glucocorticoid-induced...
Cancer immunotherapy is finally entering a new era with manipulation of cosignaling pathways as a therapeutic approach, for which the principle was proved nearly two decades ago. In addition to CTLA-4, CD137 and B7-H1/PD-1 pathways are two new targets in the stage. CD137 pathway is costimulatory and its agonistic antibody delivers potent signal to drive T cell growth and activation. On the other hand,...
LAG-3 (CD223) is a cell surface molecule expressed on activated T cells (Huard et al. Immunogenetics 39:213–217, 1994), NK cells (Triebel et al. J Exp Med 171:1393–1405, 1990), B cells (Kisielow et al. Eur J Immunol 35:2081–2088, 2005), and plasmacytoid dendritic cells (Workman et al. J Immunol 182:1885–1891, 2009) that plays an important but incompletely understood role in the function of these lymphocyte...
Our understanding of immunological regulation has progressed tremendously alongside the development of materials science, and at their intersection emerges the possibility to employ immunologically active biomaterials for cancer immunotherapy. Strong and sustained anticancer, immune responses are required to clear large tumor burdens in patients, but current approaches for immunotherapy are formulated...
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