title: Mesothelioma response to carbon nanotubes is associated with an early and selective accumulation of immunosuppressive monocytic cells.
abstract: The asbestos-like toxicity of some engineered carbon nanotubes (CNT), notably their capacity to induce mesothelioma, is a serious cause of concern for public health. Here we show that carcinogenic CNT induce an early and sustained immunosuppressive response characterized by the accumulation of monocytic Myeloid Derived Suppressor Cells (M-MDSC) that counteract effective immune surveillance of tumor cells.
  
  
  
  Wistar rats and C57BL/6 mice were intraperitoneally injected with carcinogenic multi-walled Mitsui-7 CNT (CNT-7) or crocidolite asbestos. Peritoneal mesothelioma development and immune cell accumulation were assessed until 12 months. Leukocyte sub-populations were identified by recording expression of CD11b/c and His48 by flow cytometry. The immunosuppressive activity on T lymphocytes of purified peritoneal leukocytes was assessed in a co-culture assay with activated spleen cells.
  
  
  
  We demonstrate that long and short mesotheliomagenic CNT-7 injected in the peritoneal cavity of rats induced, like asbestos, an early and selective accumulation of monocytic cells (CD11b/c(int) and His48(hi)) which possess the ability to suppress polyclonal activation of T lymphocytes and correspond to M-MDSC. Peritoneal M-MDSC persisted during the development of peritoneal mesothelioma in CNT-7-treated rats but were only transiently recruited after non-carcinogenic CNT (CNT-M, CNT-T) injection. Peritoneal M-MDSC did not accumulate in mice which are resistant to mesothelioma development.
  
  
  
  Our data provide new insights into the initial pathogenic events induced by CNT, adding a new component to the adverse outcome pathway leading to mesothelioma development. The specificity of the M-MDSC response after carcinogenic CNT exposure highlights the interest of this response for detecting the ability of new nanomaterials to cause cancer.
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain, Avenue Mounier 53 bte B1.52.12, 1200, Brussels, Belgium. francois.huaux@uclouvain.be.
authors.forename: François
authors.initials: F
authors.lastname: Huaux
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain, Avenue Mounier 53 bte B1.52.12, 1200, Brussels, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: d'Ursel de Bousies
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain, Avenue Mounier 53 bte B1.52.12, 1200, Brussels, Belgium.
authors.forename: Marie-Astrid
authors.initials: MA
authors.lastname: Parent
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain, Avenue Mounier 53 bte B1.52.12, 1200, Brussels, Belgium.
authors.forename: Micaela
authors.initials: M
authors.lastname: Orsi
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain, Avenue Mounier 53 bte B1.52.12, 1200, Brussels, Belgium.
authors.forename: Francine
authors.initials: F
authors.lastname: Uwambayinema
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain, Avenue Mounier 53 bte B1.52.12, 1200, Brussels, Belgium.
authors.forename: Raynal
authors.initials: R
authors.lastname: Devosse
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain, Avenue Mounier 53 bte B1.52.12, 1200, Brussels, Belgium.
authors.forename: Saloua
authors.initials: S
authors.lastname: Ibouraadaten
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain, Avenue Mounier 53 bte B1.52.12, 1200, Brussels, Belgium.
authors.forename: Yousof
authors.initials: Y
authors.lastname: Yakoub
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain, Avenue Mounier 53 bte B1.52.12, 1200, Brussels, Belgium.
authors.forename: Nadtha
authors.initials: N
authors.lastname: Panin
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain, Avenue Mounier 53 bte B1.52.12, 1200, Brussels, Belgium.
authors.forename: Mihaly
authors.initials: M
authors.lastname: Palmai-Pallag
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch, de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: van der Bruggen
authors.affiliation: Bio and Soft Matter (BSMA), Institute of Condensed Matter and Nanosciences (IMCN), Université catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Bailly
authors.affiliation: Departement of Chemistry, Université de Namur, Namur, Belgium.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Marega
authors.affiliation: de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Marbaix
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain, Avenue Mounier 53 bte B1.52.12, 1200, Brussels, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D064593:Heterografts; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000139:chemically induced* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D037742:Nanotubes, Carbon / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002273:Carcinogens; D037742:Nanotubes, Carbon
keywords: Asbestos; Carbon nanotubes; Crocidolite; Fibers; Immunosuppression; Inflammation; Mesothelioma; Myeloid cells; Rats and mice