ORCID Profile
0000-0003-0042-7955
Current Organisation
Fondazione IRCCS Istituto Nazionale dei Tumori
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Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22423014.V1
Abstract: selective gene expression alterations in p50-/- M-MDSC stimulated with IFNγ for 4 hours as compared to WT M-MDSC
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22423005
Abstract: Association of each induced gene to the nearest STAT1 peak according to the distance between the TSS (Transcription Start Site) of each gene and the summit of STAT1 induced peaks.
Publisher: Oxford University Press (OUP)
Date: 19-12-2017
DOI: 10.1093/IBD/IZX024
Abstract: DUOX2 and DUOXA2 form the predominant H2O2-producing system in human colorectal mucosa. Inflammation, hypoxia, and 5-aminosalicylic acid increase H2O2 production, supporting innate defense and mucosal healing. Thiocyanate reacts with H2O2 in the presence of lactoperoxidase (LPO) to form hypothiocyanate (OSCN-), which acts as a biocide and H2O2 scavenging system to reduce damage during inflammation. We aimed to discover the organization of Duox2, Duoxa2, and Lpo expression in colonic crypts of Lieberkühn (intestinal glands) of mice and how distributions respond to dextran sodium sulfate (DSS)-induced colitis and subsequent mucosal regeneration. We studied tissue from DSS-exposed mice and human biopsies using in situ hybridization, reverse transcription quantitative polymerase chain reaction, and cDNA microarray analysis. Duox2 mRNA expression was mostly in the upper crypt quintile while Duoxa2 was more apically focused. Most Lpo mRNA was in the basal quintile, where stem cells reside. Duox2 and Duoxa2 mRNA were increased during the induction and resolution of DSS colitis, while Lpo expression did not increase during the acute phase. Patterns of Lpo expression differed from Duox2 in normal, inflamed, and regenerative mouse crypts (P & 0.001). We found no evidence of LPO expression in the human gut. The spatial and temporal separation of H2O2-consuming and -producing enzymes enables a thiocyanate- H2O2 “scavenging” system in murine intestinal crypts to protect the stem roliferative zones from DNA damage, while still supporting higher H2O2 concentrations apically to aid mucosal healing. The absence of LPO expression in the human gut suggests an alternative mechanism or less protection from DNA damage during H2O2-driven mucosal healing.
Publisher: American Association for Cancer Research (AACR)
Date: 07-2020
DOI: 10.1158/0008-5472.CAN-19-2843
Abstract: Tumor-derived PGE2-mediated induction of nuclear p50 NF-κB epigenetically reprograms the response of monocytic cells to IFNγ toward an immunosuppressive phenotype, thus retrieving the anticancer properties of IFNγ.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22423017
Abstract: supplementary figures and Materials & Methods
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22423008
Abstract: Stat1 peaks detected in p50-/- PEC stimulated with IFNγ for 2 hours as compared to WT PEC
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22423014
Abstract: selective gene expression alterations in p50-/- M-MDSC stimulated with IFNγ for 4 hours as compared to WT M-MDSC
Publisher: American Society for Clinical Investigation
Date: 15-04-2003
DOI: 10.1172/JCI200317426
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22423008.V1
Abstract: Stat1 peaks detected in p50-/- PEC stimulated with IFNγ for 2 hours as compared to WT PEC
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.C.6511398.V1
Abstract: Abstract Myeloid-derived suppressor cells (MDSC) include immature monocytic (M-MDSC) and granulocytic (PMN-MDSC) cells that share the ability to suppress adaptive immunity and to hinder the effectiveness of anticancer treatments. Of note, in response to IFNγ, M-MDSCs release the tumor-promoting and immunosuppressive molecule nitric oxide (NO), whereas macrophages largely express antitumor properties. Investigating these opposing activities, we found that tumor-derived prostaglandin E2 (PGE2) induces nuclear accumulation of p50 NF-κB in M-MDSCs, erting their response to IFNγ toward NO-mediated immunosuppression and reducing TNFα expression. At the genome level, p50 NF-κB promoted binding of STAT1 to regulatory regions of selected IFNγ-dependent genes, including inducible nitric oxide synthase (Nos2). In agreement, ablation of p50 as well as pharmacologic inhibition of either the PGE2 receptor EP2 or NO production reprogrammed M-MDSCs toward a NOS2 sup low /sup /TNFα sup high /sup phenotype, restoring the i in vivo /i antitumor activity of IFNγ. Our results indicate that inhibition of the PGE2 50/NO axis prevents MDSC-suppressive functions and restores the efficacy of anticancer immunotherapy. Significance: Tumor-derived PGE2-mediated induction of nuclear p50 NF-κB epigenetically reprograms the response of monocytic cells to IFNγ toward an immunosuppressive phenotype, thus retrieving the anticancer properties of IFNγ. /
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22423011
Abstract: selective gene expression alterations in p50-/- PEC stimulated with IFNγ for 4 hours as compared to WT PEC
Publisher: Informa UK Limited
Date: 25-02-2015
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22423005.V1
Abstract: Association of each induced gene to the nearest STAT1 peak according to the distance between the TSS (Transcription Start Site) of each gene and the summit of STAT1 induced peaks.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22423017.V1
Abstract: supplementary figures and Materials & Methods
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22423011.V1
Abstract: selective gene expression alterations in p50-/- PEC stimulated with IFNγ for 4 hours as compared to WT PEC
Location: Italy
No related grants have been discovered for Mario Paolo Colombo.