المؤلفون: Vito Longo, Carminia Maria Della Corte, Alessandro Russo, Francesca Spinnato, Francesca Ambrosio, Riccardo Ronga, Antonella Marchese, Teresa Del Giudice, Concetta Sergi, Francesca Casaluce, Marina Gilli, Michele Montrone, Valerio Gristina, Vincenzo Sforza, Maria Lucia Reale, Raimondo Di Liello, Alberto Servetto, Helga Lipari, Claudio Longhitano, Laura Vizzini, Anna Manzo, Antonella Cristofano, Loretta Paolelli, Annalisa Nardone, Simona De Summa, Antonella Perrone, Carmela Bisceglia, Caterina Derosa, Valerio Nardone, Giuseppe Viscardi, Domenico Galetta, Fabiana Vitiello

المصدر: Frontiers in Immunology, Vol 14 (2024)

مصطلحات موضوعية: consolidative radiotherapy, SCLC - small cell lung cancer, chemoimmunotherapy, innate immunity, safety, Immunologic diseases. Allergy, RC581-607

الوصف: BackgroundConsolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented.MethodsA total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy.ResultsPreclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1289434/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/0916d9972ccf47d690c1cb596c1e055dTest

المؤلفون: Thomas Clarke, Pan Du, Satyendra Kumar, Shinji L. Okitsu, Mark Schuette, Qi An, Jinyang Zhang, Evgeni Tzvetkov, Mark A. Jensen, Timothy B. Niewold, Elise M. N. Ferre, Julie Nardone, Michail S. Lionakis, Jaromir Vlach, Julie DeMartino, Andrew T. Bender

المصدر: Frontiers in Immunology, Vol 14 (2023)

مصطلحات موضوعية: autoantibody, autoimmune disease (AD), autoimmune polyendocrinopathy candidiasis ecotodermal dystrophy (APECED), B cell receptor (BCR), Sjogren's syndrome, systemic lupus erythematosus (SLE), Immunologic diseases. Allergy, RC581-607

الوصف: Autoimmune diseases vary in the magnitude and diversity of autoantibody profiles, and these differences may be a consequence of different types of breaks in tolerance. Here, we compared the disparate autoimmune diseases autoimmune polyendocrinopathy–candidiasis–ecto-dermal dystrophy (APECED), systemic lupus erythematosus (SLE), and Sjogren’s syndrome (SjS) to gain insight into the etiology of breaks in tolerance triggering autoimmunity. APECED was chosen as a prototypical monogenic disease with organ-specific pathology while SjS and SLE represent polygenic autoimmunity with focal or systemic disease. Using protein microarrays for autoantibody profiling, we found that APECED patients develop a focused but highly reactive set of shared mostly anti-cytokine antibodies, while SLE patients develop broad and less expanded autoantibody repertoires against mostly intracellular autoantigens. SjS patients had few autoantibody specificities with the highest shared reactivities observed against Ro-52 and La. RNA-seq B-cell receptor analysis revealed that APECED samples have fewer, but highly expanded, clonotypes compared with SLE samples containing a diverse, but less clonally expanded, B-cell receptor repertoire. Based on these data, we propose a model whereby the presence of autoreactive T-cells in APECED allows T-dependent B-cell responses against autoantigens, while SLE is driven by breaks in peripheral B-cell tolerance and extrafollicular B-cell activation. These results highlight differences in the autoimmunity observed in several monogenic and polygenic disorders and may be generalizable to other autoimmune diseases.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1106537/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/e823a778e94642ba916ed495ae37f622Test

المؤلفون: Alessandra Ruggiero, Giuseppe Rubens Pascucci, Nicola Cotugno, Sara Domínguez-Rodríguez, Stefano Rinaldi, Alfredo Tagarro, Pablo Rojo, Caroline Foster, Alasdair Bamford, Anita De Rossi, Eleni Nastouli, Nigel Klein, Elena Morrocchi, Benoit Fatou, Kinga K. Smolen, Al Ozonoff, Michela Di Pastena, Katherine Luzuriaga, Hanno Steen, Carlo Giaquinto, Philip Goulder, Paolo Rossi, Ofer Levy, Savita Pahwa, Paolo Palma, the EPIICAL Consortium, Mark Cotton, Shaun Barnabas, Thanyawee Puthanakit, Louise Kuhn, Andrew Yates, Avy Violari, Kennedy Otwombe, Paula Vaz, Maria Grazia Lain, Tacilta Nampossa, Denise Naniche, Sheila Fernandez-Luis, Elisa Lopez, Holly Peay, Moira Spyer, Vincent Calvez, Anne-Genevieve Marcelin, Maria Angeles Munoz, Annalisa Dalzini, Raffaella Petrara, Kathleen Gartner, Lesley De Armas, Pahwa Rajendra, Suresh Pallikkuth, Deborah Persaud, Nicolas Chomont, Mathias Lichterfeld, Silvia Faggion, Daniel Gomez Pena, Andrea Oletto, Alessandra Nardone, Paola Zangari, Silvia Di Cesare, Chiara Medri, Olga Kolesova, Carla Paganin, William James, Inger Lindfors - Rossi, Shrabon Samiur Hassan, Francesca Mazzetto, Hellen Akisinku, Musakanya Chingandu, Francesca Rocchi, Ilaria Pepponi, Rob J. De Boer, Juliane Schroter, Viviana Giannuzzi, Sinead Morris

المصدر: Frontiers in Immunology, Vol 13 (2022)

مصطلحات موضوعية: T-bet, CD11c, perinatal HIV/AIDS, B-cell hyperactivation, proteomic profiling immune activation, late ART, Immunologic diseases. Allergy, RC581-607

الوصف: BackgroundDespite a successful antiretroviral therapy (ART), adolescents living with perinatally acquired HIV (PHIV) experience signs of B-cell hyperactivation with expansion of ‘namely’ atypical B-cell phenotypes, including double negative (CD27-IgD-) and termed age associated (ABCs) B-cells (T-bet+CD11c+), which may result in reduced cell functionality, including loss of vaccine-induced immunological memory and higher risk of developing B-cells associated tumors. In this context, perinatally HIV infected children (PHIV) deserve particular attention, given their life-long exposure to chronic immune activation.MethodsWe studied 40 PHIV who started treatment by the 2nd year of life and maintained virological suppression for 13.5 years, with 5/40 patients experiencing transient elevation of the HIV-1 load in the plasma (Spike). We applied a multi-disciplinary approach including immunological B and T cell phenotype, plasma proteomics analysis, and serum level of anti-measles antibodies as functional correlates of vaccine-induced immunity.ResultsPhenotypic signs of B cell hyperactivation were elevated in subjects starting ART later (%DN T-bet+CD11c+ p=0.03; %AM T-bet+CD11c+ p=0.02) and were associated with detectable cell-associated HIV-1 RNA (%AM T-bet+CD11c+ p=0.0003) and transient elevation of the plasma viral load (spike). Furthermore, B-cell hyperactivation appeared to be present in individuals with higher frequency of exhausted T-cells, in particular: %CD4 TIGIT+ were associated with %DN (p=0.008), %DN T-bet+CD11c+ (p=0.0002) and %AM T-bet+CD11c+ (p=0.002) and %CD4 PD-1 were associated with %DN (p=0.048), %DN T-bet+CD11c+ (p=0.039) and %AM T-bet+CD11c+ (p=0.006). The proteomic analysis revealed that subjects with expansion of these atypical B-cells and exhausted T-cells had enrichment of proteins involved in immune inflammation and complement activation pathways. Furthermore, we observed that higher levels of ABCs were associated a reduced capacity to maintain vaccine-induced antibody immunity against measles (%B-cells CD19+CD10- T-bet+, p=0.035).ConclusionWe identified that the levels of hyperactivated B cell subsets were strongly affected by time of ART start and associated with clinical, viral, cellular and plasma soluble markers. Furthermore, the expansion of ABCs also had a direct impact on the capacity to develop antibodies response following routine vaccination.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2022.860418/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/4c3438cc6e094cf89b7fa756b480c8baTest

المؤلفون: Zingoni, A, Vulpis, E, Cecere, F, Amendola, MG, Fuerst, D, Saribekyan, T, Achour, A, Sandalova, T, Nardone, I, Peri, A, Soriani, A, Fionda, C, Mariggo, E, Petrucci, MT, Ricciardi, MR, Mytilineos, J, Cippitelli, M, Cerboni, C, Santoni, A

المصدر: Frontiers in immunology. 9:926

مصطلحات موضوعية: Medicin och hälsovetenskap

الوصول الحر: http://kipublications.ki.se/Default.aspx?queryparsed=id:138156007Test

المؤلفون: Guido Villani, Fabiana Castiglione, Franco Scaldaferri, Anna Testa, Roberto de Sire, Valentina Petito, Olga Maria Nardone

المساهمون: Nardone, O. M., de Sire, R., Petito, V., Testa, A., Villani, G., Scaldaferri, F., Castiglione, F.

المصدر: Frontiers in Immunology, Vol 12 (2021)
Frontiers in Immunology

مصطلحات موضوعية: 0301 basic medicine, Sarcopenia, Review, Gut flora, Bioinformatics, Inflammatory bowel disease, Pathogenesis, 0302 clinical medicine, Immunology and Allergy, gut-muscle axi, Intestinal Mucosa, Inflammation Mediator, biology, 030211 gastroenterology & hepatology, Inflammation Mediators, medicine.symptom, probiotic, Human, Signal Transduction, Settore MED/12 - GASTROENTEROLOGIA, IBD, Immunology, Inflammation, malnutrition, digestive system, 03 medical and health sciences, Immune system, Insulin resistance, medicine, Animals, Humans, gut-muscle axis, Muscle, Skeletal, gut microbiota, Bacteria, Animal, business.industry, Inflammatory Bowel Disease, muscle wasting, RC581-607, Inflammatory Bowel Diseases, medicine.disease, biology.organism_classification, digestive system diseases, Dysbiosi, Gastrointestinal Microbiome, Malnutrition, 030104 developmental biology, probiotics, inflammation, Dysbiosis, Immunologic diseases. Allergy, business

الوصف: Sarcopenia represents a major health burden in industrialized country by reducing substantially the quality of life. Indeed, it is characterized by a progressive and generalized loss of muscle mass and function, leading to an increased risk of adverse outcomes and hospitalizations. Several factors are involved in the pathogenesis of sarcopenia, such as aging, inflammation, mitochondrial dysfunction, and insulin resistance. Recently, it has been reported that more than one third of inflammatory bowel disease (IBD) patients suffered from sarcopenia. Notably, the role of gut microbiota (GM) in developing muscle failure in IBD patient is a matter of increasing interest. It has been hypothesized that gut dysbiosis, that typically characterizes IBD, might alter the immune response and host metabolism, promoting a low-grade inflammation status able to up-regulate several molecular pathways related to sarcopenia. Therefore, we aim to describe the basis of IBD-related sarcopenia and provide the rationale for new potential therapeutic targets that may regulate the gut-muscle axis in IBD patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::689645018545b35f8de12dcfe1fff4ebTest
https://doi.org/10.3389/fimmu.2021.694217Test

المؤلفون: Valerio Nardone, Pierpaolo Pastina, Rocco Giannicola, Rita Agostino, Stefania Croci, Paolo Tini, Luigi Pirtoli, Antonio Giordano, Pierosandro Tagliaferri, Pierpaolo Correale

المساهمون: Nardone, V, Pastina, P, Giannicola, R, Agostino, R, Croci, S, Tini, P, Pirtoli, L, Giordano, A, Tagliaferri, Pierosandro, Correale, Pierpaolo

المصدر: Frontiers in Immunology, Vol 9 (2018)
Frontiers in Immunology

مصطلحات موضوعية: 0301 basic medicine, Oncology, lcsh:Immunologic diseases. Allergy, Opinion, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, Immunology, NSCLC, chemotherapy, radiation therapy, HNSCC, 03 medical and health sciences, 0302 clinical medicine, Text mining, Drug Therapy, immunotherapy, Carcinoma, Non-Small-Cell Lung, Internal medicine, medicine, Humans, Immunology and Allergy, Chemotherapy, Radiotherapy, business.industry, Immunotherapy, Combined Modality Therapy, Radiation therapy, Treatment Outcome, 030104 developmental biology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Non small lung cancer, business, lcsh:RC581-607

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c265c308177e7a5d85d9a49f54e974b2Test
https://www.frontiersin.org/article/10.3389/fimmu.2018.02941/fullTest

المؤلفون: Nardone, Olga Maria, de Sire, Roberto, Petito, Valentina, Testa, Anna, Villani, Guido, Scaldaferri, Franco, Castiglione, Fabiana

المصدر: Frontiers in Immunology; 7/13/2021, Vol. 12, p1-11, 11p

مصطلحات موضوعية: INFLAMMATORY bowel diseases, MUSCLE growth, GUT microbiome, SARCOPENIA, DRUG target

مستخلص: Sarcopenia represents a major health burden in industrialized country by reducing substantially the quality of life. Indeed, it is characterized by a progressive and generalized loss of muscle mass and function, leading to an increased risk of adverse outcomes and hospitalizations. Several factors are involved in the pathogenesis of sarcopenia, such as aging, inflammation, mitochondrial dysfunction, and insulin resistance. Recently, it has been reported that more than one third of inflammatory bowel disease (IBD) patients suffered from sarcopenia. Notably, the role of gut microbiota (GM) in developing muscle failure in IBD patient is a matter of increasing interest. It has been hypothesized that gut dysbiosis, that typically characterizes IBD, might alter the immune response and host metabolism, promoting a low-grade inflammation status able to up-regulate several molecular pathways related to sarcopenia. Therefore, we aim to describe the basis of IBD-related sarcopenia and provide the rationale for new potential therapeutic targets that may regulate the gut-muscle axis in IBD patients. [ABSTRACT FROM AUTHOR]

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المؤلفون: Alessandra Zingoni, Elisabetta Vulpis, Francesca Cecere, Maria G. Amendola, Daniel Fuerst, Taron Saribekyan, Adnane Achour, Tatyana Sandalova, Ilaria Nardone, Agnese Peri, Alessandra Soriani, Cinzia Fionda, Elena Mariggiò, Maria T. Petrucci, Maria R. Ricciardi, Joannis Mytilineos, Marco Cippitelli, Cristina Cerboni, Angela Santoni

المصدر: Frontiers in Immunology
Frontiers in Immunology, Vol 9 (2018)

مصطلحات موضوعية: 0301 basic medicine, Male, Models, Molecular, Protein Conformation, Genotype, Immunology and Allergy, Receptor, predictive biomarker, Original Research, Aged, 80 and over, natural killer cells, biology, Chemistry, Middle Aged, Immunosurveillance, Gene Expression Regulation, Neoplastic, Killer Cells, Natural, multiple myeloma, NK Cell Lectin-Like Receptor Subfamily K, Disease Progression, Female, NKG2D receptor, Protein Binding, lcsh:Immunologic diseases. Allergy, Immunology, Enzyme-Linked Immunosorbent Assay, MICA polymorphism, Immunophenotyping, 03 medical and health sciences, Structure-Activity Relationship, Immune system, MHC class I, Humans, Genetic Predisposition to Disease, Alleles, Genetic Association Studies, Aged, Polymorphism, Genetic, Histocompatibility Antigens Class I, NKG2D, Molecular biology, Molecular Typing, stomatognathic diseases, 030104 developmental biology, Amino Acid Substitution, Tumor progression, biology.protein, multiple myeloma, natural killer cells, NKG2D receptor, MICA polymorphism, predictive biomarker, Gene polymorphism, lcsh:RC581-607

الوصف: Natural killer (NK) cells are immune innate effectors playing a pivotal role in the immunosurveillance of multiple myeloma (MM) since they are able to directly recognize and kill MM cells. In this regard, among activating receptors expressed by NK cells, NKG2D represents an important receptor for the recognition of MM cells, being its ligands expressed by tumor cells, and being able to trigger NK cell cytotoxicity. The MHC class I-related molecule A (MICA) is one of the NKG2D ligands; it is encoded by highly polymorphic genes and exists as membrane-bound and soluble isoforms. Soluble MICA (sMICA) is overexpressed in the serum of MM patients, and its levels correlate with tumor progression. Interestingly, a methionine (Met) to valine (Val) substitution at position 129 of the α2 heavy chain domain classifies the MICA alleles into strong (MICA-129Met) and weak (MICA-129Val) binders to NKG2D receptor. We addressed whether the genetic polymorphisms in the MICA-129 alleles could affect MICA release during MM progression. The frequencies of Val/Val, Val/Met, and Met/Met MICA-129 genotypes in a cohort of 137 MM patients were 36, 43, and 22%, respectively. Interestingly, patients characterized by a Val/Val genotype exhibited the highest levels of sMICA in the sera. In addition, analysis of the frequencies of MICA-129 genotypes among different MM disease states revealed that Val/Val patients had a significant higher frequency of relapse. Interestingly, NKG2D was downmodulated in NK cells derived from MICA-129Met/Met MM patients. Results obtained by structural modeling analysis suggested that the Met to Val dimorphism could affect the capacity of MICA to form an optimal template for NKG2D recognition. In conclusion, our findings indicate that the MICA-129Val/Val variant is associated with significantly higher levels of sMICA and the progression of MM, strongly suggesting that the usage of soluble MICA as prognostic marker has to be definitely combined with the patient MICA genotype.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d4fc1b4f4eef9a21a3808c2d42c2e120Test

المؤلفون: Olga Maria Nardone, Roberto de Sire, Valentina Petito, Anna Testa, Guido Villani, Franco Scaldaferri, Fabiana Castiglione

المصدر: Frontiers in Immunology, Vol 12 (2021)

مصطلحات موضوعية: IBD, sarcopenia, gut-muscle axis, gut microbiota, probiotics, inflammation, Immunologic diseases. Allergy, RC581-607

الوصف: Sarcopenia represents a major health burden in industrialized country by reducing substantially the quality of life. Indeed, it is characterized by a progressive and generalized loss of muscle mass and function, leading to an increased risk of adverse outcomes and hospitalizations. Several factors are involved in the pathogenesis of sarcopenia, such as aging, inflammation, mitochondrial dysfunction, and insulin resistance. Recently, it has been reported that more than one third of inflammatory bowel disease (IBD) patients suffered from sarcopenia. Notably, the role of gut microbiota (GM) in developing muscle failure in IBD patient is a matter of increasing interest. It has been hypothesized that gut dysbiosis, that typically characterizes IBD, might alter the immune response and host metabolism, promoting a low-grade inflammation status able to up-regulate several molecular pathways related to sarcopenia. Therefore, we aim to describe the basis of IBD-related sarcopenia and provide the rationale for new potential therapeutic targets that may regulate the gut-muscle axis in IBD patients.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2021.694217/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/33e0d4f8135f4a62b5d38ba6702f06fcTest