title: T cells contribute to tumor progression by favoring pro-tumoral properties of intra-tumoral myeloid cells in a mouse model for spontaneous melanoma.
abstract: Tumors affect myelopoeisis and induce the expansion of myeloid cells with immunosuppressive activity. In the MT/ret model of spontaneous metastatic melanoma, myeloid cells are the most abundant tumor infiltrating hematopoietic population and their proportion is highest in the most aggressive cutaneous metastasis. Our data suggest that the tumor microenvironment favors polarization of myeloid cells into type 2 cells characterized by F4/80 expression, a weak capacity to secrete IL-12 and a high production of arginase. Myeloid cells from tumor and spleen of MT/ret mice inhibit T cell proliferation and IFNγ secretion. Interestingly, T cells play a role in type 2 polarization of myeloid cells. Indeed, intra-tumoral myeloid cells from MT/ret mice lacking T cells are not only less suppressive towards T cells than corresponding cells from wild-type MT/ret mice, but they also inhibit more efficiently melanoma cell proliferation. Thus, our data support the existence of a vicious circle, in which T cells may favor cancer development by establishing an environment that is likely to skew myeloid cell immunity toward a tumor promoting response that, in turn, suppresses immune effector cell functions.
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France.
authors.forename: Renée
authors.initials: R
authors.lastname: Lengagne
authors.forename: Arnaud
authors.initials: A
authors.lastname: Pommier
authors.forename: Jonathan
authors.initials: J
authors.lastname: Caron
authors.forename: Laetitia
authors.initials: L
authors.lastname: Douguet
authors.forename: Marylène
authors.initials: M
authors.lastname: Garcette
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Avril
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Abastado
authors.forename: Nadège
authors.initials: N
authors.lastname: Bercovici
authors.forename: Bruno
authors.initials: B
authors.lastname: Lucas
authors.forename: Armelle
authors.initials: A
authors.lastname: Prévost-Blondel
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008668:Metallothionein / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D000943:Antigens, Differentiation; D039481:CD11b Antigen; C036763:monocyte-macrophage differentiation antigen; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D008668:Metallothionein; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human