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

F Ghiringhelli, PE Puig, S Roux, A Parcellier… - The Journal of …, 2005 - rupress.org
F Ghiringhelli, PE Puig, S Roux, A Parcellier, E Schmitt, E Solary, G Kroemer, F Martin…
The Journal of experimental medicine, 2005rupress.org
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)–β receptor II. During tumor progression,
a subset of dendritic cells (DCs) exhibiting a myeloid immature phenotype is recruited to …
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)–β 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-β–dependent manner in mice and rats. Tumor cells are necessary and sufficient to convert DCs into regulatory cells that secrete bioactive TGF-β and stimulate T reg cell proliferation. In conclusion, tumor expansion can stimulate T reg cells via a specific DC subset.
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