title: Inflammatory blood monocytes contribute to tumor development and represent a privileged target to improve host immunosurveillance.
abstract: Progressing tumors in humans and mice are frequently infiltrated by a highly heterogeneous population of inflammatory myeloid cells that contribute to tumor growth. Among these cells, inflammatory Gr-1(+) monocytes display a high developmental plasticity in response to specific microenvironmental signals, leading to diverse immune functions. These observations raise the question of the immune mechanisms by which inflammatory monocytes may contribute to tumor development. In this study, we found that adoptive transfer of normal inflammatory Gr-1(+) monocytes in tumor-bearing mice promotes tumor growth. In this tumoral environment, these monocytes can differentiate into tolerogenic dendritic cells (DCs) that produce IL-10 and potently induce regulatory T cell responses in vivo. Moreover, diverting the differentiation of Gr-1(+) monocytes into tolerogenic DCs by forced expression of IL-10 soluble receptor and IL-3 in tumor cells improves host immunosurveillance by reducing the regulatory T cell frequency and by inducing immunogenic DCs in the tumor. As a consequence, tumor growth is strongly reduced. Our findings indicate that Gr-1(+) monocytes represent a valuable target for innovative immunotherapeutic strategies against cancer.
authors.affiliation: Centre National de la Recherche Scientifique, GEPITOS, Unité Mixte de Recherche 6235, Nice, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Augier
authors.forename: Thomas
authors.initials: T
authors.lastname: Ciucci
authors.forename: Carmelo
authors.initials: C
authors.lastname: Luci
authors.forename: Georges F
authors.initials: GF
authors.lastname: Carle
authors.forename: Claudine
authors.initials: C
authors.lastname: Blin-Wakkach
authors.forename: Abdelilah
authors.initials: A
authors.lastname: Wakkach
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance; D007157:Immunologic Surveillance; D016753:Interleukin-10 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology
chemical_list: D016753:Interleukin-10