{"title":"Glycan diversity in ovarian cancer: Unraveling the immune interplay and therapeutic prospects.","authors":"Gerrit Wolters-Eisfeld, Leticia Oliveira-Ferrer","doi":"10.1007/s00281-024-01025-6","DOIUrl":"10.1007/s00281-024-01025-6","url":null,"abstract":"<p><p>Ovarian cancer remains a formidable challenge in oncology due to its late-stage diagnosis and limited treatment options. Recent research has revealed the intricate interplay between glycan diversity and the immune microenvironment within ovarian tumors, shedding new light on potential therapeutic strategies. This review seeks to investigate the complex role of glycans in ovarian cancer and their impact on the immune response. Glycans, complex sugar molecules decorating cell surfaces and secreted proteins, have emerged as key regulators of immune surveillance in ovarian cancer. Aberrant glycosylation patterns can promote immune evasion by shielding tumor cells from immune recognition, enabling disease progression. Conversely, certain glycan structures can modulate the immune response, leading to either antitumor immunity or immune tolerance. Understanding the intricate relationship between glycan diversity and immune interactions in ovarian cancer holds promise for the development of innovative therapeutic approaches. Immunotherapies that target glycan-mediated immune evasion, such as glycan-based vaccines or checkpoint inhibitors, are under investigation. Additionally, glycan profiling may serve as a diagnostic tool for patient stratification and treatment selection. This review underscores the emerging importance of glycan diversity in ovarian cancer, emphasizing the potential for unraveling immune interplay and advancing tailored therapeutic prospects for this devastating disease.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142474222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paolo Rosales, Daiana Vitale, Antonella Icardi, Ina Sevic, Laura Alaniz
{"title":"Role of Hyaluronic acid and its chemical derivatives in immunity during homeostasis, cancer and tissue regeneration.","authors":"Paolo Rosales, Daiana Vitale, Antonella Icardi, Ina Sevic, Laura Alaniz","doi":"10.1007/s00281-024-01024-7","DOIUrl":"10.1007/s00281-024-01024-7","url":null,"abstract":"<p><p>Over the last few decades, scientists have recognized the critical role that various components of the extracellular matrix (ECM) play in maintaining homeostatic immunity. Besides, dysregulation in the synthesis or degradation levels of these components directly impacts the mechanisms of immune response during tissue injury caused by tumor processes or the regeneration of the tissue itself in the event of damage. ECM is a complex network of protein compounds, proteoglycans and glycosaminoglycans (GAGs). Hyaluronic acid (HA) is one of the major GAGs of this network, whose metabolism is strictly physiologically regulated and quickly altered in injury processes, affecting the behavior of different cells, from stem cells to differentiated immune cells. In this revision we discuss how the native or chemically modified HA interacts with its specific receptors and modulates intra and intercellular communication of immune cells, focusing on cancer and tissue regeneration conditions.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The fetal programming effect of maternal immune activation (MIA) on the offspring's immune system.","authors":"Naomi Hofsink, Lucianne Groenink, Torsten Plösch","doi":"10.1007/s00281-024-01023-8","DOIUrl":"10.1007/s00281-024-01023-8","url":null,"abstract":"<p><p>The first 1000 days of life is a critical period of development in which adverse circumstances can have long-term consequences for the child's health. Maternal immune activation is associated with increased risk of neurodevelopmental disorders in the child. Aberrant immune responses have been reported in individuals with neurodevelopmental disorders. Moreover, lasting effects of maternal immune activation on the offspring's immune system have been reported. Taken together, this indicates that the effect of maternal immune activation is not limited to the central nervous system. Here, we explore the impact of maternal immune activation on the immune system of the offspring. We first describe the development of the immune system and provide an overview of reported alterations in the cytokine profiles, immune cell profiles, immune cell function, and immune induction in pre-clinical models. Additionally, we highlight recent research on the impact of maternal COVID-19 exposure on the neonatal immune system and the potential health consequences for the child. Our review shows that maternal immune activation alters the offspring's immune system under certain conditions, but the reported effects are conflicting and inconsistent. In general, epigenetic modifications are considered the mechanism for fetal programming. The available data was insufficient to identify specific pathways that may contribute to immune programming. As a consequence of the COVID-19 pandemic, more research now focuses on the possible health effects of maternal immune activation on the offspring. Future research addressing the offspring's immune response to maternal immune activation can elucidate specific pathways that contribute to fetal immune programming and the long-term health effects for the offspring.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11364800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ole Bæk, Frederik Schaltz-Buchholzer, Anita Campbell, Nelly Amenyogbe, James Campbell, Peter Aaby, Christine Stabell Benn, Tobias R Kollmann
{"title":"The mark of success: The role of vaccine-induced skin scar formation for BCG and smallpox vaccine-associated clinical benefits.","authors":"Ole Bæk, Frederik Schaltz-Buchholzer, Anita Campbell, Nelly Amenyogbe, James Campbell, Peter Aaby, Christine Stabell Benn, Tobias R Kollmann","doi":"10.1007/s00281-024-01022-9","DOIUrl":"10.1007/s00281-024-01022-9","url":null,"abstract":"<p><p>Skin scar formation following Bacille Calmette-Guérin (BCG) or smallpox (Vaccinia) vaccination is an established marker of successful vaccination and 'vaccine take'. Potent pathogen-specific (tuberculosis; smallpox) and pathogen-agnostic (protection from diseases unrelated to the intentionally targeted pathogen) effects of BCG and smallpox vaccines hold significant translational potential. Yet despite their use for centuries, how scar formation occurs and how local skin-based events relate to systemic effects that allow these two vaccines to deliver powerful health promoting effects has not yet been determined. We review here what is known about the events occurring in the skin and place this knowledge in the context of the overall impact of these two vaccines on human health with a particular focus on maternal-child health.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advances in manufacturing chimeric antigen receptor immune cell therapies.","authors":"Apoorva Ramamurthy, Anna Tommasi, Krishanu Saha","doi":"10.1007/s00281-024-01019-4","DOIUrl":"10.1007/s00281-024-01019-4","url":null,"abstract":"<p><p>Biomedical research has witnessed significant strides in manufacturing chimeric antigen receptor T cell (CAR-T) therapies, marking a transformative era in cellular immunotherapy. Nevertheless, existing manufacturing methods for autologous cell therapies still pose several challenges related to cost, immune cell source, safety risks, and scalability. These challenges have motivated recent efforts to optimize process development and manufacturing for cell therapies using automated closed-system bioreactors and models created using artificial intelligence. Simultaneously, non-viral gene transfer methods like mRNA, CRISPR genome editing, and transposons are being applied to engineer T cells and other immune cells like macrophages and natural killer cells. Alternative sources of primary immune cells and stem cells are being developed to generate universal, allogeneic therapies, signaling a shift away from the current autologous paradigm. These multifaceted innovations in manufacturing underscore a collective effort to propel this therapeutic approach toward broader clinical adoption and improved patient outcomes in the evolving landscape of cancer treatment. Here, we review current CAR immune cell manufacturing strategies and highlight recent advancements in cell therapy scale-up, automation, process development, and engineering.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Victoria Bazzano, Angela Köninger, Maria Emilia Solano
{"title":"Beyond defence: Immune architects of ovarian health and disease.","authors":"Maria Victoria Bazzano, Angela Köninger, Maria Emilia Solano","doi":"10.1007/s00281-024-01021-w","DOIUrl":"10.1007/s00281-024-01021-w","url":null,"abstract":"<p><p>Throughout the individual's reproductive period of life the ovary undergoes continues changes, including cyclic processes of cell death, tissue regeneration, proliferation, and vascularization. Tissue-resident leucocytes particularly macrophages, play a crucial role in shaping ovarian function and maintaining homeostasis. Macrophages crucially promote angiogenesis in the follicles and corpora lutea, thereby supporting steroidogenesis. Recent research on macrophage origins and early tissue seeding has unveiled significant insights into their role in early organogenesis, e.g. in the testis. Here, we review evidence about the prenatal ovarian seeding of leucocytes, primarily macrophages with angiogenic profiles, and its connection to gametogenesis. In the prenatal ovary, germ cells proliferate, form cysts, and undergo changes that, following waves of apoptosis, give rice to the oocytes contained in primordial follicles. These follicles constitute the ovarian reserve that lasts throughout the female's reproductive life. Simultaneously, yolk-sac-derived primitive macrophages colonizing the early ovary are gradually replaced or outnumbered by monocyte-derived fetal macrophages. However, the cues indicating how macrophage colonization and follicle assembly are related are elusive. Macrophages may contribute to organogenesis by promoting early vasculogenesis. Whether macrophages contribute to ovarian lymphangiogenesis or innervation is still unknown. Ovarian organogenesis and gametogenesis are vulnerable to prenatal insults, potentially programming dysfunction in later life, as observed in polycystic ovary syndrome. Experimental and, more sparsely, epidemiological evidence suggest that adverse stimuli during pregnancy can program defective folliculogenesis or a diminished follicle reserve in the offspring. While the ovary is highly sensitive to inflammation, the involvement of local immune responses in programming ovarian health and disease remains to be thoroughly investigated.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ajmal Ahmad, Anneliesse Braden, Sazzad Khan, Jianfeng Xiao, Mohammad Moshahid Khan
{"title":"Crosstalk between the DNA damage response and cellular senescence drives aging and age-related diseases.","authors":"Ajmal Ahmad, Anneliesse Braden, Sazzad Khan, Jianfeng Xiao, Mohammad Moshahid Khan","doi":"10.1007/s00281-024-01016-7","DOIUrl":"10.1007/s00281-024-01016-7","url":null,"abstract":"<p><p>Cellular senescence is a crucial process of irreversible cell-cycle arrest, in which cells remain alive, but permanently unable to proliferate in response to distinct types of stressors. Accumulating evidence suggests that DNA damage builds over time and triggers DNA damage response signaling, leading to cellular senescence. Cellular senescence serves as a platform for the perpetuation of inflammatory responses and is central to numerous age-related diseases. Defects in DNA repair genes or senescence can cause premature aging disease. Therapeutic approaches limiting DNA damage or senescence contribute to a rescued phenotype of longevity and neuroprotection, thus suggesting a mechanistic interaction between DNA damage and senescence. Here, we offer a unique perspective on the crosstalk between the DNA damage response pathway and senescence as well as their contribution to age-related diseases. We further summarize recent progress on the mechanisms and therapeutics of senescence, address existing challenges, and offering new insights and future directions in the senescence field.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Early-life risk factors which govern pro-allergic immunity","authors":"Catherine Ptaschinski, Bernhard F. Gibbs","doi":"10.1007/s00281-024-01020-x","DOIUrl":"https://doi.org/10.1007/s00281-024-01020-x","url":null,"abstract":"<p>Allergic diseases affect up to 40% of the global population with a substantial rise in food allergies, in particular, over the past decades. For the majority of individuals with allergy fundamental programming of a pro-allergic immune system largely occurs in early childhood where it is crucially governed by prenatal genetic and environmental factors, including their interactions. These factors include several genetic aberrations, such as filaggrin loss-of-function mutations, early exposure to respiratory syncytial virus, and various chemicals such as plasticizers, as well as the influence of the gut microbiome and numerous lifestyle circumstances. The effects of such a wide range of factors on allergic responses to an array of potential allergens is complex and the severity of these responses in a clinical setting are subsequently not easy to predict at the present time. However, some parameters which condition a pro-allergic immune response, including severe anaphylaxis, are becoming clearer. This review summarises what we currently know, and don’t know, about the factors which influence developing pro-allergic immunity particularly during the early-life perinatal period.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141770172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anaisa V Ferreira, Jorge Domínguez-Andrés, Laura M Merlo Pich, Leo A B Joosten, Mihai G Netea
{"title":"Metabolic Regulation in the Induction of Trained Immunity.","authors":"Anaisa V Ferreira, Jorge Domínguez-Andrés, Laura M Merlo Pich, Leo A B Joosten, Mihai G Netea","doi":"10.1007/s00281-024-01015-8","DOIUrl":"10.1007/s00281-024-01015-8","url":null,"abstract":"<p><p>The innate immune system exhibits features of memory, termed trained immunity, which promote faster and more robust responsiveness to heterologous challenges. Innate immune memory is sustained through epigenetic modifications, affecting gene accessibility, and promoting a tailored gene transcription for an enhanced immune response. Alterations in the epigenetic landscape are intertwined with metabolic rewiring. Here, we review the metabolic pathways that underscore the induction and maintenance of trained immunity, including glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, and amino acid and lipid metabolism. The intricate interplay of these pathways is pivotal for establishing innate immune memory in distinct cellular compartments. We explore in particular the case of resident lung alveolar macrophages. We propose that leveraging the memory of the innate immune system may present therapeutic potential. Specifically, targeting the metabolic programs of innate immune cells is an emerging strategy for clinical interventions, either to boost immune responses in immunosuppressed conditions or to mitigate maladaptive activation in hyperinflammatory diseases.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martina Spiga, Elisa Martini, Maria Chiara Maffia, Fabio Ciceri, Eliana Ruggiero, Alessia Potenza, Chiara Bonini
{"title":"Harnessing the tumor microenvironment to boost adoptive T cell therapy with engineered lymphocytes for solid tumors.","authors":"Martina Spiga, Elisa Martini, Maria Chiara Maffia, Fabio Ciceri, Eliana Ruggiero, Alessia Potenza, Chiara Bonini","doi":"10.1007/s00281-024-01011-y","DOIUrl":"10.1007/s00281-024-01011-y","url":null,"abstract":"<p><p>Adoptive cell therapy (ACT) using Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR) engineered T cells represents an innovative therapeutic approach for the treatment of hematological malignancies, yet its application for solid tumors is still suboptimal. The tumor microenvironment (TME) places several challenges to overcome for a satisfactory therapeutic effect, such as physical barriers (fibrotic capsule and stroma), and inhibitory signals impeding T cell function. Some of these obstacles can be faced by combining ACT with other anti-tumor approaches, such as chemo/radiotherapy and checkpoint inhibitors. On the other hand, cutting edge technological tools offer the opportunity to overcome and, in some cases, take advantage of TME intrinsic characteristics to boost ACT efficacy. These include: the exploitation of chemokine gradients and integrin expression for preferential T-cell homing and extravasation; metabolic changes that have direct or indirect effects on TCR-T and CAR-T cells by increasing antigen presentation and reshaping T cell phenotype; introduction of additional synthetic receptors on TCR-T and CAR-T cells with the aim of increasing T cells survival and fitness.</p>","PeriodicalId":21704,"journal":{"name":"Seminars in Immunopathology","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}