Regulatory T cells and tumor immunity

Abstract

Central deletion of "self-reactive" T cells has been the textbook paradigm for inducing "self-tolerance" in the periphery and the concept of a role of T cell-mediated suppression in this process has long been controversial. A decisive shift in the opinion on suppressor T cells has lately occurred with the observations of Sakaguchi's group that linked a class of CD4+CD25+ T cells to the prevention of autoimmunity from neonatal thymectomy in mice. These CD4+CD25+ T cells have been named T regulatory (Treg) cells. They are believed to be selected in the thymus as an anti-self repertoire. Hence they were referred to as natural T regulatory (nTreg) cells. Presently, in addition to their role in autoimmunity, they are believed to exert regulatory function in infection, in transplantation immunity as well as in tumor immunity. In contrast to these nTreg cells, another class of CD4+ Treg cells also exercises regulatory function in the periphery. These Treg cells are also CD4+ T cells and after activation they also become phenotypically CD4+CD25+. They are, however induced in the periphery as Treg cells. Hence, they are termed as induced Treg (iTreg) cells. There are major differences in the biology of these two types of Treg cells. They differ in their requirements for activation and in their mode of action. Nonetheless, evidence indicates that both nTreg cells and iTreg cells are involved in the control of tumor immunity. The question of how to circumvent their regulatory constraints, therefore, has become a major challenge for tumor immunologists.

Effects of the Administration of High-Dose Interleukin-2 on Immunoregulatory Cell Subsets in Patients with Advanced Melanoma and Renal Cell Cancer

“…+ regulatory T cells have been observed in melanoma and various other types of cancer (14,15) and are associated with reduced survival (16), a recent study evaluated whether depletion of CD4 + CD25 + regulatory T cells using recombinant IL-2 diphtheria toxin (DAB 389 IL-2) would enhance tumor-specific T-cell responses in patients with RCC, as indicated by earlier reports in mice (17), and found that this was indeed the case (18).…”

1,25-Dihydroxyvitamin D3 inhibits proliferation but not the suppressive function of regulatory T cells in the absence of antigen-presenting cells

“…Over the past decade, evidence has mounted for the potential therapeutic application of Treg cells either in enhancing their regulatory activity in inflammatory diseases such as autoimmunity, allograft rejection, graft versus host disease and allergic diseases, or in blocking their suppressive activity in tumour immunity or vaccine development. [15][16][17][18] Either Treg cells can be derived from the thymus, the so-called naturally occurring Treg (nTreg) cells, or they can be induced de novo in the periphery from CD4 + T cells. Vitamin D 3 interferes with the maturation and differentiation of dendritic cells and may induce a so-called tolerogenic phenotype.…”

CD4+CD25+FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas

“…There is increasing evidence for the existence of elevated numbers of regulatory T-cells in solid tumors and hematological malignancies [1][2][3][4][5][6][7][8][9][10]. The presence of infiltrating Treg may be detrimental to the host defense against the tumor, while the presence of effector T lymphocytes, including CD8 + and nonregulatory CD4…”