title: Disrupted lymph node and splenic stroma in mice with induced inflammatory melanomas is associated with impaired recruitment of T and dendritic cells.
abstract: Migration of dendritic cells (DC) from the tumor environment to the T cell cortex in tumor-draining lymph nodes (TDLN) is essential for priming naïve T lymphocytes (TL) to tumor antigen (Ag). We used a mouse model of induced melanoma in which similar oncogenic events generate two phenotypically distinct melanomas to study the influence of tumor-associated inflammation on secondary lymphoid organ (SLO) organization. One tumor promotes inflammatory cytokines, leading to mobilization of immature myeloid cells (iMC) to the tumor and SLO; the other does not. We report that inflammatory tumors induced alterations of the stromal cell network of SLO, profoundly altering the distribution of TL and the capacity of skin-derived DC and TL to migrate or home to TDLN. These defects, which did not require tumor invasion, correlated with loss of fibroblastic reticular cells in T cell zones and in impaired production of CCL21. Infiltrating iMC accumulated in the TDLN medulla and the splenic red pulp. We propose that impaired function of the stromal cell network during chronic inflammation induced by some tumors renders spleens non-receptive to TL and TDLN non-receptive to TL and migratory DC, while the entry of iMC into these perturbed SLO is enhanced. This could constitute a mechanism by which inflammatory tumors escape immune control. If our results apply to inflammatory tumors in general, the demonstration that SLO are poorly receptive to CCR7-dependent migration of skin-derived DC and naïve TL may constitute an obstacle for proposed vaccination or adoptive TL therapies of their hosts.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, UMR6546, Marseille, France.
authors.forename: Saïdi M
authors.initials: SM
authors.lastname: Soudja
authors.forename: Sandrine
authors.initials: S
authors.lastname: Henri
authors.forename: Marielle
authors.initials: M
authors.lastname: Mello
authors.forename: Lionel
authors.initials: L
authors.lastname: Chasson
authors.forename: Amandine
authors.initials: A
authors.lastname: Mas
authors.forename: Maria
authors.initials: M
authors.lastname: Wehbe
authors.forename: Nathalie
authors.initials: N
authors.lastname: Auphan-Anezin
authors.forename: Lee
authors.initials: L
authors.lastname: Leserman
authors.forename: Benoît
authors.initials: B
authors.lastname: Van den Eynde
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Schmitt-Verhulst
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D054421:Chemokine CCL21 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology*; D008545:Melanoma / Q000150:complications / Q000276:immunology / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000473:pathology; D012878:Skin Neoplasms / Q000150:complications / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology*; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D000098853:Podoplanin
chemical_list: D039481:CD11b Antigen; D054421:Chemokine CCL21; D008562:Membrane Glycoproteins; C490441:Pdpn protein, mouse; D000098853:Podoplanin