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

By François Ghiringhelli, P. Puig, S. Roux, Arnaud Parcellier, E. Schmitt, E. Solary, Guido Kroemer, F. Martin, B. Chauffert, L. Zitvogel. Journal of Experimental Medicine, 2005

824 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/b72c928a1e114ffd93c1a4934d4d38443b62c2ed

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In Immunology

1. Guido Kroemer
2. L. Zitvogel
3. R. Flavell
4. C. Lewis
5. Shomyseh Sanjabi
6. P. Puig
7. F. Martin
8. Craig Murdoch

Citations in the corpus

• Cancer despite immunosurveillance: immunoselection and immunosubversion (2006, background): “Recent data also indicate that a specific subset of tumour-associated DCs can stimulate the proliferation of T Reg cells in a TGFβ-dependent manne”
• Transforming Grown Factor-β Signaling in Immunity and Cancer (2019, neutral): “In tumor models, cancer cells instruct DCs to secrete TGF-β, which in turn promotes acquisition of a Treg phenotype by CD4+ T cells (Dumitriu et al., 2009; Ghiringhelli et al., 2005).”
• The polarization of immune cells in the tumour environment by TGFβ (2010, background): “So, in the context of these immunosuppressive cytokines in the tumour microenvironment, DCs take up tumour cells, become tolerogenic TGFβ-secreting cells and promote the induction of tumour-specific T Reg cells in both mice and human”
• Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients (2007, background): “We reported recently that tumor cells could drive immature dendritic cells to express TGF- required for local expansion of Treg [5].”
• T Regulatory Cells: Key Players in Tumor Immune Escape and Angiogenesis (2012, background): “Our recent discovery that Tregs secrete VEGF (3), a known immunosuppressive molecule, adds to the panel of paracrine mechanisms through which Treg can exert suppression and affect the differentiation and function of DCs.”
• Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects (2020, background): “On the one hand, MDSCs induced by tumour progression selectively promoted the proliferation of Tregs in a TGF-β-dependent manner in vivo [56], and”
• Myeloid derived suppressor cells promote cross-tolerance in B cell lymphoma by expanding regulatory T cells (2008, background): “responsible for Treg expansion, both intratumorally and in the draining lymph nodes (35).”