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The immune system is comprised of a network of regulatory and effector mechanisms that is balanced to eliminate threats to the body, while preventing uncontrolled inflammatory and auto-immune responses that would otherwise harm self. T regulatory (Treg) cells are central to this process and are required to maintain self-tolerance by actively inhibiting self-reactive T cells by a variety of direct and indirect mechanisms. Numerous studies have shown that Treg cells also exist in tumors, promote a suppressive environment that interferes with antitumor immunity, and are a major barrier to successful immunotherapy. In this review we will discuss evidence for how different types of CD4+ Treg cells are involved in antitumor immunity in both mice and humans. We also highlight strategies that have successfully inhibited Treg cells in animal models of cancer and in human clinical trials. In addition, the known effects of Treg cells on current immunotherapy approaches will be discussed. A better understanding of how Treg cells hinder antitumor immunity is required to optimize current therapeutic regimens and to make effective cancer immunotherapy a reality for an increased number of patients. [ABSTRACT FROM AUTHOR]

Regulatory T cells play a central role in controlling homeostasis, and in inducing and maintaining tolerance to both foreign and self-antigens. Several types of T cells with regulatory activity have been described both in mice and humans, and those within the CD4+ subset have been extensively studied. Among them, the best characterized are the naturally occurring CD4+CD25+ regulatory T (Treg) cells, and the adaptive type 1 regulatory T (Tr1) cells. Natural Treg cells can arise directly from the thymus, are characterized by the constitutive expression of the transcription factor Foxp3, and suppress T cell responses in a cell-cell contact mediated mechanism. On the contrary, adaptive Tr1 cells arise in the periphery upon encountering antigen in a tolerogenic environment, produce high levels of interleukin (IL)-10 and mediate suppression via IL-10. During the last decade, much effort has been placed on developing protocols to generate regulatory T-cell lines and clones, to further define the similarities and differences between various regulatory T-cell subsets. In this chapter, we will outline protocols to expand naturally occurring Treg cells, to differentiate homogeneous population of Tr1 cells in vitro, and to generate natural Treg and Tr1 cell clones and cell lines. [ABSTRACT FROM AUTHOR]