title: An immunosurveillance mechanism controls cancer cell ploidy.
abstract: Cancer cells accommodate multiple genetic and epigenetic alterations that initially activate intrinsic (cell-autonomous) and extrinsic (immune-mediated) oncosuppressive mechanisms. Only once these barriers to oncogenesis have been overcome can malignant growth proceed unrestrained. Tetraploidization can contribute to oncogenesis because hyperploid cells are genomically unstable. We report that hyperploid cancer cells become immunogenic because of a constitutive endoplasmic reticulum stress response resulting in the aberrant cell surface exposure of calreticulin. Hyperploid, calreticulin-exposing cancer cells readily proliferated in immunodeficient mice and conserved their increased DNA content. In contrast, hyperploid cells injected into immunocompetent mice generated tumors only after a delay, and such tumors exhibited reduced DNA content, endoplasmic reticulum stress, and calreticulin exposure. Our results unveil an immunosurveillance system that imposes immunoselection against hyperploidy in carcinogen- and oncogene-induced cancers.
authors.affiliation: INSERM, U848, Villejuif, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Senovilla
authors.forename: Ilio
authors.initials: I
authors.lastname: Vitale
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martins
authors.forename: Maximilien
authors.initials: M
authors.lastname: Tailler
authors.forename: Claire
authors.initials: C
authors.lastname: Pailleret
authors.forename: Mickaël
authors.initials: M
authors.lastname: Michaud
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.forename: Sandy
authors.initials: S
authors.lastname: Adjemian
authors.forename: Oliver
authors.initials: O
authors.lastname: Kepp
authors.forename: Mireia
authors.initials: M
authors.lastname: Niso-Santano
authors.forename: Shensi
authors.initials: S
authors.lastname: Shen
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mariño
authors.forename: Alfredo
authors.initials: A
authors.lastname: Criollo
authors.forename: Alice
authors.initials: A
authors.lastname: Boilève
authors.forename: Bastien
authors.initials: B
authors.lastname: Job
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ladoire
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
authors.forename: Antonella
authors.initials: A
authors.lastname: Sistigu
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Santiago
authors.initials: S
authors.lastname: Rello-Varona
authors.forename: Clara
authors.initials: C
authors.lastname: Locher
authors.forename: Vichnou
authors.initials: V
authors.lastname: Poirier-Colame
authors.forename: Monique
authors.initials: M
authors.lastname: Talbot
authors.forename: Alexander
authors.initials: A
authors.lastname: Valent
authors.forename: Francesco
authors.initials: F
authors.lastname: Berardinelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Antoccia
authors.forename: Fabiola
authors.initials: F
authors.lastname: Ciccosanti
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Fimia
authors.forename: Mauro
authors.initials: M
authors.lastname: Piacentini
authors.forename: Antonio
authors.initials: A
authors.lastname: Fueyo
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Messina
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Chan
authors.forename: Verena
authors.initials: V
authors.lastname: Sigl
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pourcher
authors.forename: Christoph
authors.initials: C
authors.lastname: Ruckenstuhl
authors.forename: Didac
authors.initials: D
authors.lastname: Carmona-Gutierrez
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lazar
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Otín
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Maria
authors.initials: M
authors.lastname: Castedo
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D037282:Calreticulin / Q000276:immunology; D045744:Cell Line, Tumor; D017074:Common Variable Immunodeficiency / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000276:immunology*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006801:Humans; D007121:Immunocompetence; D007157:Immunologic Surveillance; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D010766:Phosphorylation; D011003:Ploidies
chemical_list: D037282:Calreticulin; D004273:DNA, Neoplasm; D015852:Eukaryotic Initiation Factor-2