Foxp3 expressing CD4+CD25high regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells

Manuelle Viguier, Fabrice Lemaître, Olivier Verola, Min Sun Cho, Guy Gorochov, Louis Dubertret, Hervé Bachelez, Philippe Kourilsky, Laurent Ferradini

Research output: Contribution to journalArticlepeer-review

632 Scopus citations

Abstract

Dominant tolerance is mediated by regulatory T cells (Treg) that control harmful autoimmune T cells àn in the periphery. In this study, we investigate the implication of Treg in modulating infiltrating T lymphocytes in human metastatic melanoma. We found that CD4+CD25 high T cells are overrepresented in metastatic lymph nodes (LNs) with a 2-fold increased frequency compared with both tumor-free LNs and autologous PBMCs. These cells express the Foxp3 transcription factor, display an activated phenotype, and display a polyclonal TCR Vβ chain repertoire. They inhibit in vitro the proliferation and cytokine production of infiltrating CD4 +CD25- and CD8+ T cells (IL-2, IFN-γ) through a cell-contact-dependent mechanism, thus behaving as Treg. In some cases, the presence of Treg type 1/Th3-like lymphocytes could also be demonstrated. Thus, Treg are a major component of the immunosuppressive microenvironment of metastatic melanoma LNs. This could explain the poor clinical response of cancer patients under immunotherapeutic protocols, and provides a new basis for future immunotherapeutic strategies counteracting in vivo Treg to reinforce local antitumor immune responses.

Original languageEnglish
Pages (from-to)1444-1453
Number of pages10
JournalJournal of Immunology
Volume173
Issue number2
DOIs
StatePublished - 15 Jul 2004

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