title: Depletion of Regulatory T Cells Induces High Numbers of Dendritic Cells and Unmasks a Subset of Anti-Tumour CD8+CD11c+ PD-1lo Effector T Cells.
abstract: Natural regulatory T (Treg) cells interfere with multiple functions, which are crucial for the development of strong anti-tumour responses. In a model of 4T1 mammary carcinoma, depletion of CD25+Tregs results in tumour regression in Balb/c mice, but the mechanisms underlying this process are not fully understood. Here, we show that partial Treg depletion leads to the generation of a particular effector CD8 T cell subset expressing CD11c and low level of PD-1 in tumour draining lymph nodes. These cells have the capacity to migrate into the tumour, to kill DCs, and to locally regulate the anti-tumour response. These events are concordant with a substantial increase in CD11b+ resident dendritic cells (DCs) subsets in draining lymph nodes followed by CD8+ DCs. These results indicate that Treg depletion leads to tumour regression by unmasking an increase of DC subsets as a part of a program that optimizes the microenvironment by orchestrating the activation, amplification, and migration of high numbers of fully differentiated CD8+CD11c+PD1lo effector T cells to the tumour sites. They also indicate that a critical pattern of DC subsets correlates with the evolution of the anti-tumour response and provide a template for Treg depletion and DC-based therapy.
authors.affiliation: Plateau technique de Cytometrie et d'Imagerie Cellulaire, Structure Fédérative de Recherche Necker, INSERM US 24-CNRS, UMS 3633, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Goudin
authors.affiliation: Institut Necker Enfants Malades, INSERM U1151, CNRS, UMR8253, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Chappert
authors.affiliation: Plateau technique de Cytometrie et d'Imagerie Cellulaire, Structure Fédérative de Recherche Necker, INSERM US 24-CNRS, UMS 3633, Paris, France.
authors.forename: Jérome
authors.initials: J
authors.lastname: Mégret
authors.affiliation: Institut Necker Enfants Malades, INSERM U1151, CNRS, UMR8253, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Gross
authors.affiliation: Institut Necker Enfants Malades, INSERM U1151, CNRS, UMR8253, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Benedita
authors.initials: B
authors.lastname: Rocha
authors.affiliation: Institut Necker Enfants Malades, INSERM U1151, CNRS, UMR8253, Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Orly
authors.identifier: http://orcid.org/0000-0003-2503-6299
authors.initials: O
authors.lastname: Azogui