Tumor cells convert immature myeloid dendritic cells into TGF-β–secreting cells inducing CD4 + CD25 + regulatory T cell proliferation

作者：François Ghiringhelli, Pierre E. Puig, S. Roux, Arnaud Parcellier, Elise Schmitt, Éric Solary, Guido Kroemer, François Martin, Bruno Chauffert, Laurence Zitvogel · 发表于：The Journal of Experimental Medicine · 年份：2005 · DOI：10.1084/jem.20050463 · 被引用次数：790 · 研究领域：T-cell and B-cell Immunology、Immunotherapy and Immune Responses、Immune Cell Function and Interaction

The mechanisms through which regulatory T cells accumulate in lymphoid organs of tumor-bearing hosts remain elusive. Our experiments indicate that the accumulation of CD4+CD25+ regulatory T cells (T reg cells) expressing FoxP3 and exhibiting immunosuppressive function originates from the proliferation of naturally occurring CD25+ T cells and requires signaling through transforming growth factor (TGF)-beta receptor II. During tumor progression, a subset of dendritic cells (DCs) exhibiting a myeloid immature phenotype is recruited to draining lymph nodes. This DC subset selectively promotes the proliferation of T reg cells in a TGF-beta-dependent manner in mice and rats. Tumor cells are necessary and sufficient to convert DCs into regulatory cells that secrete bioactive TGF-beta and stimulate T reg cell proliferation. In conclusion, tumor expansion can stimulate T reg cells via a specific DC subset.