المؤلفون: Macchia, Iole, La Sorsa, Valentina, Urbani, Francesca, Moretti, Sonia, Antonucci, Caterina, Afferni, Claudia, Schiavoni, Giovanna

المساهمون: Associazione Italiana per la Ricerca sul Cancro

المصدر: Frontiers in Immunology ; volume 14 ; ISSN 1664-3224

الوصف: Eosinophils are bone marrow-derived granulocytes that, under homeostatic conditions, account for as much as 1-3% of peripheral blood leukocytes. During inflammation, eosinophils can rapidly expand and infiltrate inflamed tissues, guided by cytokines and alarmins (such as IL-33), adhesion molecules and chemokines. Eosinophils play a prominent role in allergic asthma and parasitic infections. Nonetheless, they participate in the immune response against respiratory viruses such as respiratory syncytial virus and influenza. Notably, respiratory viruses are associated with asthma exacerbation. Eosinophils release several molecules endowed with antiviral activity, including cationic proteins, RNases and reactive oxygen and nitrogen species. On the other hand, eosinophils release several cytokines involved in homeostasis maintenance and Th2-related inflammation. In the context of SARS-CoV-2 infection, emerging evidence indicates that eosinophils can represent possible blood-based biomarkers for diagnosis, prognosis, and severity prediction of disease. In particular, eosinopenia seems to be an indicator of severity among patients with COVID-19, whereas an increased eosinophil count is associated with a better prognosis, including a lower incidence of complications and mortality. In the present review, we provide an overview of the role and plasticity of eosinophils focusing on various respiratory viral infections and in the context of viral and allergic disease comorbidities. We will discuss the potential utility of eosinophils as prognostic/predictive immune biomarkers in emerging respiratory viral diseases, particularly COVID-19. Finally, we will revisit some of the relevant methods and tools that have contributed to the advances in the dissection of various eosinophil subsets in different pathological settings for future biomarker definition.

الإتاحة: https://doi.org/10.3389/fimmu.2023.1170035Test

المؤلفون: Mattei, Fabrizio, Andreone, Sara, Spadaro, Francesca, Noto, Francesco, Tinari, Antonella, Falchi, Mario, Piconese, Silvia, Afferni, Claudia, Schiavoni, Giovanna

المساهمون: Mattei, Fabrizio, Andreone, Sara, Spadaro, Francesca, Noto, Francesco, Tinari, Antonella, Falchi, Mario, Piconese, Silvia, Afferni, Claudia, Schiavoni, Giovanna

مصطلحات موضوعية: biophysic, cancer, cell biology, immunology

الوصف: Trogocytosis is a cellular process whereby a cell acquires a membrane fragment from a donor cell in a contact-dependent manner allowing for the transfer of surface proteins with functional integrity. It is involved in various biological processes, including cell-cell communication, immune regulation, and response to pathogens and cancer cells, with poorly defined molecular mechanisms. With the exception of eosinophils, trogocytosis has been reported in most immune cells and plays diverse roles in the modulation of anti-tumor immune responses. Here, we report that eosinophils acquire membrane fragments from tumor cells early after contact through the CD11b/CD18 integrin complex. We discuss the impact of trogocytosis in innate immune cells on cancer progression in the context of the evidence that eosinophils can engage in trogocytosis with tumor cells. We also discuss shared and cell-specific mechanisms underlying this process based on in silico modeling and provide a hypothetical molecular model for the stabilization of the immunological synapse operating in granulocytes and possibly other innate immune cells that enables trogocytosis.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36185368; info:eu-repo/semantics/altIdentifier/wos/WOS:000869007300005; volume:25; issue:10; numberofpages:21; journal:ISCIENCE; https://hdl.handle.net/11573/1656116Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85138400626

الإتاحة: https://doi.org/10.1016/j.isci.2022.105110Test
https://hdl.handle.net/11573/1656116Test

المؤلفون: Musella, Martina, Guarracino, Andrea, Manduca, Nicoletta, Galassi, Claudia, Ruggiero, Eliana, Potenza, Alessia, Maccafeo, Ester, Manic, Gwenola, Mattiello, Luca, Soliman Abdel Rehim, Sara, Signore, Michele, Pietrosanto, Marco, Helmer-Citterich, Manuela, Pallocca, Matteo, Fanciulli, Maurizio, Bruno, Tiziana, De Nicola, Francesca, Corleone, Giacomo, Di Benedetto, Anna, Ercolani, Cristiana, Pescarmona, Edoardo, Pizzuti, Laura, Guidi, Francesco, Sperati, Francesca, Vitale, Sara, Macchia, Daniele, Spada, Massimo, Schiavoni, Giovanna, Mattei, Fabrizio, De Ninno, Adele, Businaro, Luca, Lucarini, Valeria, Bracci, Laura, Aricò, Eleonora, Ziccheddu, Giovanna, Facchiano, Francesco, Rossi, Stefania, Sanchez, Massimo, Boe, Alessandra, Biffoni, Mauro, De Maria, Ruggero, Vitale, Ilio, Sistigu, Antonella

المساهمون: Musella, Martina, Guarracino, Andrea, Manduca, Nicoletta, Galassi, Claudia, Ruggiero, Eliana, Potenza, Alessia, Maccafeo, Ester, Manic, Gwenola, Mattiello, Luca, Soliman Abdel Rehim, Sara, Signore, Michele, Pietrosanto, Marco, Helmer-Citterich, Manuela, Pallocca, Matteo, Fanciulli, Maurizio, Bruno, Tiziana, De Nicola, Francesca, Corleone, Giacomo, Di Benedetto, Anna, Ercolani, Cristiana, Pescarmona, Edoardo, Pizzuti, Laura, Guidi, Francesco, Sperati, Francesca, Vitale, Sara, Macchia, Daniele, Spada, Massimo, Schiavoni, Giovanna, Mattei, Fabrizio, De Ninno, Adele, Businaro, Luca, Lucarini, Valeria, Bracci, Laura, Aricò, Eleonora, Ziccheddu, Giovanna, Facchiano, Francesco, Rossi, Stefania, Sanchez, Massimo, Boe, Alessandra, Biffoni, Mauro, De Maria, Ruggero, Vitale, Ilio, Sistigu, Antonella

مصطلحات موضوعية: cancer stem cell, ifn.i, kdm1b

الوصف: Cancer stem cells (CSCs) are a subpopulation of cancer cells endowed with high tumorigenic, chemoresistant and metastatic potential. Nongenetic mechanisms of acquired resistance are increasingly being discovered, but molecular insights into the evolutionary process of CSCs are limited. Here, we show that type I interferons (IFNs-I) function as molecular hubs of resistance during immunogenic chemotherapy, triggering the epigenetic regulator demethylase 1B (KDM1B) to promote an adaptive, yet reversible, transcriptional rewiring of cancer cells towards stemness and immune escape. Accordingly, KDM1B inhibition prevents the appearance of IFN-I-induced CSCs, both in vitro and in vivo. Notably, IFN-I-induced CSCs are heterogeneous in terms of multidrug resistance, plasticity, invasiveness and immunogenicity. Moreover, in breast cancer (BC) patients receiving anthracycline-based chemotherapy, KDM1B positively correlated with CSC signatures. Our study identifies an IFN-I -> KDM1B axis as a potent engine of cancer cell reprogramming, supporting KDM1B targeting as an attractive adjunctive to immunogenic drugs to prevent CSC expansion and increase the long-term benefit of therapy.Type I interferons have been described to have protumor or antitumor functions depending on context. Here the authors show a protumor function for type I interferons in that they promote cancer stem cells by upregulating the chromatin remodeling factor KDM1B.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36002648; info:eu-repo/semantics/altIdentifier/wos/WOS:000844434100003; volume:23; issue:9; firstpage:1379; lastpage:1392; numberofpages:14; journal:NATURE IMMUNOLOGY; https://hdl.handle.net/11573/1700275Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85136883660

الإتاحة: https://doi.org/10.1038/s41590-022-01290-3Test
https://hdl.handle.net/11573/1700275Test

المؤلفون: Gambardella, Adriana R., Poto, Remo, Tirelli, Valentina, Schroeder, John T., Marone, Gianni, Mattei, Fabrizio, Varricchi, Gilda, Schiavoni, Giovanna

المصدر: Frontiers in Immunology ; volume 13 ; ISSN 1664-3224

الوصف: Epithelial-derived alarmins (IL-33, TSLP, and IL-25) play an upstream role in the pathogenesis of asthma. Basophil-derived cytokines are a pivotal component of allergic inflammation. We evaluated the in vitro effects of IL-33, TSLP, and IL-25, alone and in combination with IL-3 on purified peripheral blood human basophils (hBaso) and bone marrow-derived mouse basophils (mBaso) in modulating the production of IL-4, IL-13, CXCL8 or the mouse CXCL8 equivalents CXCL1 and CXCL2. IL-3 and IL-33, but not TSLP and IL-25, concentration-dependently induced IL-4, IL-13, and CXCL8 release from hBaso. IL-3 synergistically potentiated the release of cytokines induced by IL-33 from hBaso. In mBaso, IL-3 and IL-33 rapidly induced IL-4 and IL-13 mRNA expression and protein release. IL-33, but not IL-3, induced CXCL2 and CXCL1 from mBaso. Differently from hBaso, TSLP induced IL-4, IL-13, CXCL1 and CXCL2 mRNA expression and protein release from mBaso. IL-25 had no effect on IL-4, IL-13, and CXCL1/CXCL2 mRNA expression and protein release even in the presence of IL-3. No synergism was observed between IL-3 and either IL-25 or TSLP. IL-3 inhibited both TSLP- and IL-33-induced CXCL1 and CXCL2 release from mBaso. Our results highlight some similarities and marked differences between the effects of IL-3 and alarmins on the release of cytokines from human and mouse basophils.

الإتاحة: https://doi.org/10.3389/fimmu.2022.894163Test

المؤلفون: Poto, Remo, Gambardella, Adriana Rosa, Marone, Gianni, Schroeder, John T., Mattei, Fabrizio, Schiavoni, Giovanna, Varricchi, Gilda

المصدر: Frontiers in Immunology ; volume 13 ; ISSN 1664-3224

الوصف: Human basophils, first identified over 140 years ago, account for just 0.5-1% of circulating leukocytes. While this scarcity long hampered basophil studies, innovations during the past 30 years, beginning with their isolation and more recently in the development of mouse models, have markedly advanced our understanding of these cells. Although dissimilarities between human and mouse basophils persist, the overall findings highlight the growing importance of these cells in health and disease. Indeed, studies continue to support basophils as key participants in IgE-mediated reactions, where they infiltrate inflammatory lesions, release pro-inflammatory mediators (histamine, leukotriene C 4 : LTC 4 ) and regulatory cytokines (IL-4, IL-13) central to the pathogenesis of allergic diseases. Studies now report basophils infiltrating various human cancers where they play diverse roles, either promoting or hampering tumorigenesis. Likewise, this activity bears remarkable similarity to the mounting evidence that basophils facilitate wound healing. In fact, both activities appear linked to the capacity of basophils to secrete IL-4/IL-13, with these cytokines polarizing macrophages toward the M2 phenotype. Basophils also secrete several angiogenic factors (vascular endothelial growth factor: VEGF-A, amphiregulin) consistent with these activities. In this review, we feature these newfound properties with the goal of unraveling the increasing importance of basophils in these diverse pathobiological processes.

الإتاحة: https://doi.org/10.3389/fimmu.2022.1056838Test

المؤلفون: Agliari, Elena, Biselli, Elena, De Ninno, Adele, Schiavoni, Giovanna, Gabriele, Lucia, Gerardino, Anna, Mattei, Fabrizio, Barra, Adriano, Businaro, Luca

المصدر: Nature Scientific Reports 4, 6639 (2014)

مصطلحات موضوعية: Quantitative Biology - Cell Behavior, Condensed Matter - Disordered Systems and Neural Networks, Physics - Biological Physics

الوصف: Scope of the present work is to frame into a rigorous, quantitative scaffold - stemmed from stochastic process theory - two sets of experiments designed to infer the spontaneous organization of leukocytes against cancer cells, namely mice splenocytes vs. B16 mouse tumor cells, and embedded in an "ad hoc" microfluidic environment developed on a LabOnChip technology. In the former, splenocytes from knocked out (KO) mice engineered to silence the transcription factor IRF-8, crucial for the development and function of several immune populations, were used. In this case lymphocytes and cancer cells exhibited a poor reciprocal exchange, resulting in the inability of coordinating or mounting an effective immune response against melanoma. In the second class of tests, wild type (WT) splenocytes were able to interact with and to coordinate a response against the tumor cells through physical interaction. The environment where cells moved was built of by two different chambers, containing respectively melanoma cells and splenocytes, connected by capillary migration channels allowing leucocytes to migrate from their chamber toward the melanoma one. We collected and analyzed data on the motility of the cells and found that the first ensemble of IRF-8 KO cells performed pure uncorrelated random walks, while WT splenocytes were able to make singular drifted random walks, that, averaged over the ensemble of cells, collapsed on a straight ballistic motion for the system as a whole. At a finer level of investigation, we found that IRF-8 KO splenocytes moved rather uniformly since their step lengths were exponentially distributed, while WT counterpart displayed a qualitatively broader motion as their step lengths along the direction of the melanoma were log-normally distributed.

الوصول الحر: http://arxiv.org/abs/1402.0451Test

المؤلفون: Macchia, Iole, La Sorsa, Valentina, Ruspantini, Irene, Sanchez, Massimo, Tirelli, Valentina, Carollo, Maria, Fedele, Giorgio, Leone, Pasqualina, Schiavoni, Giovanna, Buccione, Carla, Rizza, Paola, Nisticò, Paola, Palermo, Belinda, Morrone, Stefania, Stabile, Helena, Rughetti, Aurelia, Nuti, Marianna, Zizzari, Ilaria Grazia, Fionda, Cinzia, Maggio, Roberta, Capuano, Cristina, Quintarelli, Concetta, Sinibaldi, Matilde, Agrati, Chiara, Casetti, Rita, Rozo Gonzalez, Andrea, Iacobone, Floriana, Gismondi, Angela, Belardelli, Filippo, Biffoni, Mauro, Urbani, Francesca

المساهمون: Macchia, Iole, La Sorsa, Valentina, Ruspantini, Irene, Sanchez, Massimo, Tirelli, Valentina, Carollo, Maria, Fedele, Giorgio, Leone, Pasqualina, Schiavoni, Giovanna, Buccione, Carla, Rizza, Paola, Nisticò, Paola, Palermo, Belinda, Morrone, Stefania, Stabile, Helena, Rughetti, Aurelia, Nuti, Marianna, Zizzari, Ilaria Grazia, Fionda, Cinzia, Maggio, Roberta, Capuano, Cristina, Quintarelli, Concetta, Sinibaldi, Matilde, Agrati, Chiara, Casetti, Rita, Rozo Gonzalez, Andrea, Iacobone, Floriana, Gismondi, Angela, Belardelli, Filippo, Biffoni, Mauro, Urbani, Francesca

مصطلحات موضوعية: flow cytometry, T cell, harmonization

الوصف: Background. Personalised medicine in oncology needs standardised immunological assays. Flow cytometry (FCM) methods represent an essential tool for immunomonitoring, and their harmonisation is crucial to obtain comparable data in multicentre clinical trials. The objective of this study was to design a harmonisation workflow able to address the most effective issues contributing to intra- and interoperator variabilities in a multicentre project. Methods. The Italian National Institute of Health (Istituto Superiore di Sanita, ISS) managed a multiparametric flow cytometric panel harmonisation among thirteen operators belonging to five clinical and research centres of Lazio region (Italy). The panel was based on a backbone mixture of dried antibodies (anti-CD3, anti-CD4, anti-CD8, anti-CD45RA, and anti-CCR7) to detect naive/memory T cells, recognised as potential prognostic/predictive immunological biomarkers in cancer immunotherapies. The coordinating centre distributed frozen peripheral blood mononuclear cells (PBMCs) and fresh whole blood (WB) samples from healthy donors, reagents, and Standard Operating Procedures (SOPs) to participants who performed experiments by their own equipment, in order to mimic a real-life scenario. Operators returned raw and locally analysed data to ISS for central analysis and statistical elaboration. Results. Harmonised and reproducible results were obtained by sharing experimental set-up and procedures along with centralising data analysis, leading to a reduction of cross-centre variability for naive/memory subset frequencies particularly in the whole blood setting. Conclusion. Our experimental and analytical working process proved to be suitable for the harmonisation of FCM assays in a multicentre setting, where high-quality data are required to evaluate potential immunological markers, which may contribute to select better therapeutic options.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/32322591; info:eu-repo/semantics/altIdentifier/wos/WOS:000524295000001; volume:2020; firstpage:1; lastpage:15; numberofpages:15; journal:JOURNAL OF IMMUNOLOGY RESEARCH; http://hdl.handle.net/11573/1386510Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85083702092

الإتاحة: https://doi.org/10.1155/2020/1938704Test
http://hdl.handle.net/11573/1386510Test

المؤلفون: Mattei, Fabrizio, Andreone, Sara, Mencattini, Arianna, De Ninno, Adele, Businaro, Luca, Martinelli, Eugenio, Schiavoni, Giovanna

المساهمون: Associazione Italiana per la Ricerca sul Cancro

المصدر: Frontiers in Molecular Biosciences ; volume 8 ; ISSN 2296-889X

الوصف: Oncoimmunology represents a biomedical research discipline coined to study the roles of immune system in cancer progression with the aim of discovering novel strategies to arm it against the malignancy. Infiltration of immune cells within the tumor microenvironment is an early event that results in the establishment of a dynamic cross-talk. Here, immune cells sense antigenic cues to mount a specific anti-tumor response while cancer cells emanate inhibitory signals to dampen it. Animals models have led to giant steps in this research context, and several tools to investigate the effect of immune infiltration in the tumor microenvironment are currently available. However, the use of animals represents a challenge due to ethical issues and long duration of experiments. Organs-on-chip are innovative tools not only to study how cells derived from different organs interact with each other, but also to investigate on the crosstalk between immune cells and different types of cancer cells. In this review, we describe the state-of-the-art of microfluidics and the impact of OOC in the field of oncoimmunology underlining the importance of this system in the advancements on the complexity of tumor microenvironment.

الإتاحة: https://doi.org/10.3389/fmolb.2021.627454Test

المؤلفون: Schiavoni, Giovanna, Munitz, Ariel, Strid, Jessica

المصدر: Frontiers in Immunology ; volume 12 ; ISSN 1664-3224

مصطلحات موضوعية: Immunology, Immunology and Allergy

الإتاحة: https://doi.org/10.3389/fimmu.2021.811125Test

المؤلفون: Andreone, Sara, Gambardella, Adriana Rosa, Mancini, Jacopo, Loffredo, Stefania, Marcella, Simone, La Sorsa, Valentina, Varricchi, Gilda, Schiavoni, Giovanna, Mattei, Fabrizio

المساهمون: Associazione Italiana per la Ricerca sul Cancro

المصدر: Frontiers in Immunology ; volume 11 ; ISSN 1664-3224

الوصف: Interleukin-33 (IL-33) is an epithelial-derived cytokine that can be released upon tissue damage, stress, or infection, acting as an alarmin for the immune system. IL-33 has long been studied in the context of Th2-related immunopathologies, such as allergic diseases and parasitic infections. However, its capacity to stimulate also Th1-type of immune responses is now well established. IL-33 binds to its specific receptor ST2 expressed by most immune cell populations, modulating a variety of responses. In cancer immunity, IL-33 can display both pro-tumoral and anti-tumoral functions, depending on the specific microenvironment. Recent findings indicate that IL-33 can effectively stimulate immune effector cells (NK and CD8 + T cells), eosinophils, basophils and type 2 innate lymphoid cells (ILC2) promoting direct and indirect anti-tumoral activities. In this review, we summarize the most recent advances on anti-tumor immune mechanisms operated by IL-33, including the modulation of immune checkpoint molecules, with the aim to understand its potential as a therapeutic target in cancer.

الإتاحة: https://doi.org/10.3389/fimmu.2020.571593Test