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  1. Article ; Online: MDSCs and T cells in solid tumors and non-Hodgkin lymphomas: an immunosuppressive speech.

    Cioccarelli, Chiara / Molon, Barbara

    Clinical and experimental immunology

    2022  Volume 208, Issue 2, Page(s) 147–157

    Abstract: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous subset of cells expanded during multiple pathological settings, including cancers. In tumors, MDSCs are dominant drivers of T-cell immunosuppression. To accomplish their job, they exploit ... ...

    Abstract Myeloid-derived suppressor cells (MDSCs) are a heterogeneous subset of cells expanded during multiple pathological settings, including cancers. In tumors, MDSCs are dominant drivers of T-cell immunosuppression. To accomplish their job, they exploit multiple mechanisms ultimately leading to the paralysis of anti-tumor immunity. Among the variety of MDSC-ways of working within the tumor microenvironment, the generation of reactive species and the metabolic reprogramming have emerged as pivotal determinants of their immunosuppressive power. In this review we will overview integral mechanisms of MDSC-mediated immunosuppression in solid tumors, with a particular focus on Non-Hodgkin lymphoma.
    MeSH term(s) Humans ; Lymphoma, Non-Hodgkin/metabolism ; Lymphoma, Non-Hodgkin/pathology ; Myeloid-Derived Suppressor Cells ; Neoplasms ; Speech ; T-Lymphocytes ; Tumor Microenvironment
    Language English
    Publishing date 2022-03-29
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 218531-3
    ISSN 1365-2249 ; 0009-9104 ; 0964-2536
    ISSN (online) 1365-2249
    ISSN 0009-9104 ; 0964-2536
    DOI 10.1093/cei/uxac025
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  2. Article ; Online: COVID-19 Vaccination Limits Systemic Danger Signals in SARS-CoV-2 Infected Patients.

    Angioni, Roberta / Sasset, Lolita / Cioccarelli, Chiara / Sánchez-Rodríguez, Ricardo / Bertoldi, Nicole / Putaggio, Cristina C / Viola, Antonella / Cattelan, Annamaria / Molon, Barbara

    Viruses

    2022  Volume 14, Issue 3

    Abstract: Vaccination with an mRNA COVID-19 vaccine determines not only a consistent reduction in the risk of SARS-CoV-2 infection but also contributes to disease attenuation in infected people. Of note, hyperinflammation and damage-associated molecular patterns ( ... ...

    Abstract Vaccination with an mRNA COVID-19 vaccine determines not only a consistent reduction in the risk of SARS-CoV-2 infection but also contributes to disease attenuation in infected people. Of note, hyperinflammation and damage-associated molecular patterns (DAMPs) have been clearly associated with severe illness and poor prognosis in COVID-19 patients. In this report, we revealed a significant reduction in the levels of IL-1ß and DAMPs molecules, as S100A8 and High Mobility Group Protein B1 (HMGB1), in vaccinated patients as compared to non-vaccinated ones. COVID-19 vaccination indeed prevents severe clinical manifestations in patients and limits the release of systemic danger signals in SARS-CoV-2 infected people.
    MeSH term(s) COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; SARS-CoV-2 ; Vaccination ; Viral Vaccines
    Chemical Substances COVID-19 Vaccines ; Viral Vaccines
    Language English
    Publishing date 2022-03-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14030565
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  3. Article: STAT3 and HIF1α cooperatively mediate the transcriptional and physiological responses to hypoxia.

    Dinarello, Alberto / Betto, Riccardo Massimiliano / Diamante, Linda / Tesoriere, Annachiara / Ghirardo, Rachele / Cioccarelli, Chiara / Meneghetti, Giacomo / Peron, Margherita / Laquatra, Claudio / Tiso, Natascia / Martello, Graziano / Argenton, Francesco

    Cell death discovery

    2023  Volume 9, Issue 1, Page(s) 226

    Abstract: STAT3 and HIF1α are two fundamental transcription factors involved in many merging processes, like angiogenesis, metabolism, and cell differentiation. Notably, under pathological conditions, the two factors have been shown to interact genetically, but ... ...

    Abstract STAT3 and HIF1α are two fundamental transcription factors involved in many merging processes, like angiogenesis, metabolism, and cell differentiation. Notably, under pathological conditions, the two factors have been shown to interact genetically, but both the molecular mechanisms underlying such interactions and their relevance under physiological conditions remain unclear. In mouse embryonic stem cells (ESCs) we manage to determine the specific subset of hypoxia-induced genes that need STAT3 to be properly transcribed and, among them, fundamental genes like Vegfa, Hk1, Hk2, Pfkp and Hilpda are worth mentioning. Unexpectedly, we also demonstrated that the absence of STAT3 does not affect the expression of Hif1α mRNA nor the stabilization of HIF1α protein, but the STAT3-driven regulation of the hypoxia-dependent subset of gene could rely on the physical interaction between STAT3 and HIF1α. To further elucidate the physiological roles of this STAT3 non-canonical nuclear activity, we used a CRISPR/Cas9 zebrafish stat3 knock-out line. Notably, hypoxia-related fluorescence of the hypoxia zebrafish reporter line (HRE:mCherry) cannot be induced when Stat3 is not active and, while Stat3 Y705 phosphorylation seems to have a pivotal role in this process, S727 does not affect the Stat3-dependent hypoxia response. Hypoxia is fundamental for vascularization, angiogenesis and immune cells mobilization; all processes that, surprisingly, cannot be induced by low oxygen levels when Stat3 is genetically ablated. All in all, here we report the specific STAT3/HIF1α-dependent subset of genes in vitro and, for the first time with an in vivo model, we determined some of the physiological roles of STAT3-hypoxia crosstalk.
    Language English
    Publishing date 2023-07-05
    Publishing country United States
    Document type Journal Article
    ISSN 2058-7716
    ISSN 2058-7716
    DOI 10.1038/s41420-023-01507-w
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  4. Article ; Online: IL1β Promotes TMPRSS2 Expression and SARS-CoV-2 Cell Entry Through the p38 MAPK-GATA2 Axis.

    Cioccarelli, Chiara / Sánchez-Rodríguez, Ricardo / Angioni, Roberta / Venegas, Francisca C / Bertoldi, Nicole / Munari, Fabio / Cattelan, Annamaria / Molon, Barbara / Viola, Antonella

    Frontiers in immunology

    2021  Volume 12, Page(s) 781352

    Abstract: After the outburst of the SARS-CoV-2 pandemic, a worldwide research effort has led to the uncovering of many aspects of the COVID-19, among which we can count the outstanding role played by inflammatory cytokine milieu in the disease progression. Despite ...

    Abstract After the outburst of the SARS-CoV-2 pandemic, a worldwide research effort has led to the uncovering of many aspects of the COVID-19, among which we can count the outstanding role played by inflammatory cytokine milieu in the disease progression. Despite that, molecular mechanisms that regulate SARS-CoV-2 pathogenesis are still almost unidentified. In this study, we investigated whether the pro-inflammatory milieu of the host affects the susceptibility of SARS-CoV-2 infection by modulating
    MeSH term(s) A549 Cells ; COVID-19 ; GATA2 Transcription Factor/metabolism ; Humans ; Interleukin-1beta/metabolism ; SARS-CoV-2/pathogenicity ; Serine Endopeptidases/metabolism ; Virus Internalization ; p38 Mitogen-Activated Protein Kinases/metabolism
    Chemical Substances GATA2 Transcription Factor ; GATA2 protein, human ; IL1B protein, human ; Interleukin-1beta ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
    Language English
    Publishing date 2021-12-07
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.781352
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  5. Article ; Online: Macroplastics contamination on glaciers from Italian Central-Western Alps

    Marco Parolini / Beatrice De Felice / Chiara Lamonica / Sara Cioccarelli / Arianna Crosta / Guglielmina Diolaiuti / Marco Aldo Ortenzi / Roberto Ambrosini

    Environmental Advances, Vol 5, Iss , Pp 100084- (2021)

    2021  

    Abstract: Plastics are synthetic organic polymers playing an irreplaceable role in our everyday life. However, their massive use, improper management and end-life disposal cause plastic accumulation in the environment. Plastic contamination is ubiquitous in ... ...

    Abstract Plastics are synthetic organic polymers playing an irreplaceable role in our everyday life. However, their massive use, improper management and end-life disposal cause plastic accumulation in the environment. Plastic contamination is ubiquitous in aquatic and terrestrial ecosystems, including mountain remote areas. The present work aimed at investigating the presence of macroplastics on five glaciers of the Italian Central-Western Alps, namely Cedec and Forni glaciers (Ortles-Cevedale group) and Indren, Lys and Verra glaciers (Monte Rosa group). In late spring-summer of 2020, macroplastics were collected along normal access paths leading to some peaks of these mountain groups. In laboratory, macroplastics were sorted according to their weight, size, color, origin, usage section and polymeric composition. Macroplastics were found along all the paths, with a mean (± standard error) abundance of 18.9 ± 5.1 items per transect and an abundance per linear km ranging between 2.4 and 26.4 items/km. No significant differences of macroplastic abundance occurred between the mountain groups. Polyolefin, such as polyethylene, polystyrene and polypropylene, were the most frequent polymers contaminating glaciers, accounting for the 31% of the fingerprint, followed by polyethylene terephthalate (12%) and polyurethane (8%). The origin of most macroplastics was attributable to food packaging and items deriving from the wear of mountaineering equipment and/or clothing, which reached glacier paths through deliberate or involuntary abandonment. Virtuous behaviors aimed at limiting the abandonment of plastic waste or at collecting the items encountered on the paths should be encouraged to reduce the amount of macroplastics in remote areas.
    Keywords Plastic waste ; Glacier contamination ; High-mountain ecosystems ; Environmental sciences ; GE1-350
    Subject code 333
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: COVID-19 Vaccination Limits Systemic Danger Signals in SARS-CoV-2 Infected Patients

    Angioni, Roberta / Sasset, Lolita / Cioccarelli, Chiara / Sánchez, Ricardo / Bertoldi, Nicole / Putaggio, Cristina C. / Viola, Antonella / Cattelan, Annamaria / Molon, Barbara

    Viruses. 2022 Mar. 09, v. 14, no. 3

    2022  

    Abstract: Vaccination with an mRNA COVID-19 vaccine determines not only a consistent reduction in the risk of SARS-CoV-2 infection but also contributes to disease attenuation in infected people. Of note, hyperinflammation and damage-associated molecular patterns ( ... ...

    Abstract Vaccination with an mRNA COVID-19 vaccine determines not only a consistent reduction in the risk of SARS-CoV-2 infection but also contributes to disease attenuation in infected people. Of note, hyperinflammation and damage-associated molecular patterns (DAMPs) have been clearly associated with severe illness and poor prognosis in COVID-19 patients. In this report, we revealed a significant reduction in the levels of IL-1ß and DAMPs molecules, as S100A8 and High Mobility Group Protein B1 (HMGB1), in vaccinated patients as compared to non-vaccinated ones. COVID-19 vaccination indeed prevents severe clinical manifestations in patients and limits the release of systemic danger signals in SARS-CoV-2 infected people.
    Keywords COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; disease severity ; nucleoproteins ; prognosis ; risk ; vaccination ; vaccines
    Language English
    Dates of publication 2022-0309
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article ; Online
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14030565
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: OPA1 drives macrophage metabolism and functional commitment via p65 signaling.

    Sánchez-Rodríguez, Ricardo / Tezze, Caterina / Agnellini, Andrielly H R / Angioni, Roberta / Venegas, Francisca C / Cioccarelli, Chiara / Munari, Fabio / Bertoldi, Nicole / Canton, Marcella / Desbats, Maria Andrea / Salviati, Leonardo / Gissi, Rosanna / Castegna, Alessandra / Soriano, Maria Eugenia / Sandri, Marco / Scorrano, Luca / Viola, Antonella / Molon, Barbara

    Cell death and differentiation

    2022  Volume 30, Issue 3, Page(s) 742–752

    Abstract: Macrophages are essential players for the host response against pathogens, regulation of inflammation and tissue regeneration. The wide range of macrophage functions rely on their heterogeneity and plasticity that enable a dynamic adaptation of their ... ...

    Abstract Macrophages are essential players for the host response against pathogens, regulation of inflammation and tissue regeneration. The wide range of macrophage functions rely on their heterogeneity and plasticity that enable a dynamic adaptation of their responses according to the surrounding environmental cues. Recent studies suggest that metabolism provides synergistic support for macrophage activation and elicitation of desirable immune responses; however, the metabolic pathways orchestrating macrophage activation are still under scrutiny. Optic atrophy 1 (OPA1) is a mitochondria-shaping protein controlling mitochondrial fusion, cristae biogenesis and respiration; clear evidence shows that the lack or dysfunctional activity of this protein triggers the accumulation of metabolic intermediates of the TCA cycle. In this study, we show that OPA1 has a crucial role in macrophage activation. Selective Opa1 deletion in myeloid cells impairs M1-macrophage commitment. Mechanistically, Opa1 deletion leads to TCA cycle metabolite accumulation and defective NF-κB signaling activation. In an in vivo model of muscle regeneration upon injury, Opa1 knockout macrophages persist within the damaged tissue, leading to excess collagen deposition and impairment in muscle regeneration. Collectively, our data indicate that OPA1 is a key metabolic driver of macrophage functions.
    MeSH term(s) Mitochondria/metabolism ; Mitochondrial Membranes/metabolism ; Signal Transduction ; Macrophages/metabolism
    Language English
    Publishing date 2022-10-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225672-9
    ISSN 1476-5403 ; 1350-9047
    ISSN (online) 1476-5403
    ISSN 1350-9047
    DOI 10.1038/s41418-022-01076-y
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  8. Article ; Online: GM-CSF Nitration Is a New Driver of Myeloid Suppressor Cell Activity in Tumors.

    Calì, Bianca / Agnellini, Andrielly H R / Cioccarelli, Chiara / Sanchez-Rodriguez, Ricardo / Predonzani, Andrea / Toffolo, Giulia Ilaria / Viola, Antonella / Bronte, Vincenzo / Arrigoni, Giorgio / Zonta, Francesco / Albertoni, Laura / Mescoli, Claudia / Marigo, Ilaria / Molon, Barbara

    Frontiers in immunology

    2021  Volume 12, Page(s) 718098

    Abstract: Reactive oxygen species, including RNS, contribute to the control of multiple immune cell functions within the tumor microenvironment (TME). Tumor-infiltrating myeloid cells (TIMs) represent the archetype of tolerogenic cells that actively contribute to ... ...

    Abstract Reactive oxygen species, including RNS, contribute to the control of multiple immune cell functions within the tumor microenvironment (TME). Tumor-infiltrating myeloid cells (TIMs) represent the archetype of tolerogenic cells that actively contribute to dismantle effective immunity against cancer. TIMs inhibit T cell functions and promote tumor progression by several mechanisms including the amplification of the oxidative/nitrosative stress within the TME. In tumors, TIM expansion and differentiation is regulated by the granulocyte-macrophage colony-stimulating factor (GM-CSF), which is produced by cancer and immune cells. Nevertheless, the role of GM-CSF in tumors has not yet been fully elucidated. In this study, we show that GM-CSF activity is significantly affected by RNS-triggered post-translational modifications. The nitration of a single tryptophan residue in the sequence of GM-CSF nourishes the expansion of highly immunosuppressive myeloid subsets in tumor-bearing hosts. Importantly, tumors from colorectal cancer patients express higher levels of nitrated tryptophan compared to non-neoplastic tissues. Collectively, our data identify a novel and selective target that can be exploited to remodel the TME and foster protective immunity against cancer.
    MeSH term(s) Animals ; Biomarkers ; Cell Differentiation ; Cell Line, Tumor ; Cytokines/metabolism ; Disease Models, Animal ; Disease Susceptibility ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Immunomodulation ; Mice ; Myeloid-Derived Suppressor Cells/immunology ; Myeloid-Derived Suppressor Cells/metabolism ; Neoplasms/etiology ; Neoplasms/metabolism ; Neoplasms/pathology ; Protein Processing, Post-Translational ; Reactive Nitrogen Species/metabolism ; Signal Transduction ; Tumor Microenvironment/immunology
    Chemical Substances Biomarkers ; Cytokines ; Reactive Nitrogen Species ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
    Language English
    Publishing date 2021-10-05
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.718098
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