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Potential for stimulating host anti-tumor immune response via RNAi-mediated local FOXP3 knockdown

Cancer Gene Therapy volume 14, pages 519–520 (2007)Cite this article

Neoplastic growths represent a unique challenge for the host immune system. As they are indeed derived from self, many of the same mechanisms operating to prevent autoimmunity also provide an umbrella beneath which malignant cells are free to proliferate.1 Central among these immune regulatory boundaries are an influential subset of lymphocytes known as T regs. Hypothesized to exist decades ago, yet eluding definitive characterization until relatively recently, T regs have been demonstrated to play a crucial role in the proper functioning of the immune system as a whole. They may also, however, represent one of the primary obstacles to successful anti-tumor immunotherapies.

The T regulatory class of lymphocytes, can itself be subdivided into several distinct populations, each possessing the ability to suppress the immune response through a variety of often overlapping methods. Some of these subgroups are inducible through humoral cues present within the local microenvironment, as well as via direct cell to cell interactions. Others are assigned more permanent roles during thymic maturation. To date, the surface marker most frequently associated with thymic derived T regs, is the high-affinity α chain of the IL-2 receptor, CD25. Multiple experiments have confirmed that depletion of lymphocytes displaying this molecule leads to an increase in immune mediated tumor rejection.2, 3, 4 However, CD25 is not an absolute marker for regulatory activity in vivo. It is also found on the surface of activated effector T cells. In addition, lymphocytes capable of regulatory activity, yet lacking CD25, have been isolated.5 Thus, lympho-depletion of CD25+ cells, although offering proof of principle, may also be counterproductive owing to the elimination of potentially tumor reactive effector cells.

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  1. Department of Chemistry and Biochemistry Norfolk Virginia, Old Dominion University, Hampton, VA, USA. E-mail: nklai001@odu.edu,

    N Klaiber

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Klaiber, N. Potential for stimulating host anti-tumor immune response via RNAi-mediated local FOXP3 knockdown. Cancer Gene Ther 14, 519–520 (2007). https://doi.org/10.1038/sj.cgt.7701043

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