title: MyeloidSTAT3promotes formation of colitis-associated colorectal cancer in mice.
abstract: Myeloid cells lackingSTAT3promote antitumor responses of NK and T cells but it is unknown if this crosstalk affects development of autochthonous tumors. We deletedSTAT3in murine myeloid cells (STAT3Δm) and examined the effect on the development of autochthonous colorectal cancers (CRCs). Formation of Azoxymethane/Dextransulfate (AOM/DSS)-induced CRCs was strongly suppressed in STAT3Δmmice. Gene expression profiling showed strong activation of T cells in the stroma of STAT3ΔmCRCs. Moreover, STAT3Δmhost mice were better able to control the growth of transplanted MC38 colorectal tumor cells which are known to be killed in a T cell-dependent manner. These data suggest that myeloid cells lackingSTAT3control formation of CRCs mainly via cross activation of T cells. Interestingly, the few CRCs that formed in STAT3Δmmice displayed enhanced stromalization but appeared normal in size indicating that they have acquired ways to escape enhanced tumor surveillance. We found that CRCs in STAT3Δmmice consistently activateSTAT3signaling which is implicated in immune evasion and might be a target to prevent tumor relapse.
authors.affiliation: Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria.
authors.forename: Paulina
authors.initials: P
authors.lastname: Pathria
authors.affiliation: Institute for Pharmacology and Toxicology; University of Veterinary Medicine Vienna; Austria.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Gotthardt
authors.affiliation: Institute for Pharmacology and Toxicology; University of Veterinary Medicine Vienna; Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Prchal-Murphy
authors.affiliation: Institute for Pharmacology and Toxicology; University of Veterinary Medicine Vienna; Austria.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Putz
authors.affiliation: Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Holcmann
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research LBICR; Vienna, Austria; Institute of Clinical Pathology; Medical University of Vienna; Vienna, Austria; Unit of Pathology of Laboratory Animals; University of Veterinary Medicine Vienna ; Vienna, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Schlederer
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research LBICR; Vienna, Austria; Institute of Clinical Pathology; Medical University of Vienna; Vienna, Austria; Unit of Pathology of Laboratory Animals; University of Veterinary Medicine Vienna ; Vienna, Austria.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Grabner
authors.affiliation: Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria.
authors.forename: Ilija
authors.initials: I
authors.lastname: Crncec
authors.affiliation: Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Svinka
authors.affiliation: Spanish National Cancer Research Centre (CNIO) ; Madrid, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Musteanu
authors.affiliation: Institute of Molecular Pathology IMP ; Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoffmann
authors.affiliation: Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Filipits
authors.affiliation: Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.affiliation: Department of Molecular Biotechnology and Health Sciences; Molecular Biotechnology Center; University of Turin ; Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Poli
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research LBICR; Vienna, Austria; Institute of Clinical Pathology; Medical University of Vienna; Vienna, Austria; Unit of Pathology of Laboratory Animals; University of Veterinary Medicine Vienna ; Vienna, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Kenner
authors.affiliation: Medical University Vienna; Department of Medical and Chemical Laboratory Diagnostics ; Vienna, Austria ;
authors.forename: Martin
authors.initials: M
authors.lastname: Bilban
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research LBICR; Vienna, Austria; Institute of Clinical Pathology; Medical University of Vienna; Vienna, Austria; Unit of Pathology of Laboratory Animals; University of Veterinary Medicine Vienna ; Vienna, Austria.
authors.forename: Emilio
authors.initials: E
authors.lastname: Casanova
authors.affiliation: Institute of Animal Breeding and Genetics; University of Veterinary Medicine Vienna ; Vienna, Austria.
authors.forename: Mathias
authors.initials: M
authors.lastname: Müller
authors.affiliation: Institute of Animal Breeding and Genetics; University of Veterinary Medicine Vienna ; Vienna, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Strobl
authors.affiliation: Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria.
authors.forename: Editha
authors.initials: E
authors.lastname: Bayer
authors.affiliation: Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mohr
authors.affiliation: Institute for Pharmacology and Toxicology; University of Veterinary Medicine Vienna; Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Sexl
authors.affiliation: Institute for Cancer Research; Medical University Vienna & Comprehensive Cancer Center (CCC) ; Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Eferl
keywords: AOM, Azoxymethane, CRC, colorectal cancer; DSS, Dextransulfate; IHC, immunohistochemistry; STAT3, signal transducer and activator of transcription 3; TAM, tumor-associated macrophage; immune surveillance; immunoediting; tumor microenvironment; tumor stroma