The complexity of neutrophils in health and disease: Focus on cancer.
Abstract Neutrophils are essential soldiers of the immune response and their role have long been restricted to their activities in defence against microbial infections and during the acute phase of the inflammatory response. However, increasing number of investigations showed that neutrophils are endowed with plasticity and can participate in the orchestration of both innate and adaptive immune responses. Neutrophils have an impact on a broad range of disorders, including infections, chronic inflammations, and cancer. Neutrophils are present in the tumour microenvironment and have been reported to mediate both pro...
Source: Seminars in Immunology - September 18, 2020 Category: Allergy & Immunology Authors: Carnevale S, Ghasemi S, Rigatelli A, Jaillon S Tags: Semin Immunol Source Type: research

Prognostic significance of tumor-associated macrophages: past, present and future.
Abstract Tumor tissues are populated by a multitude of macrophages, highly different in functional activity, localization and morphology. A clear contribution to disease progression has been shown in multiple cancer types, holding promise for the development of innovative macrophage-based prognostic tools. Current studies aimed at assessing the prognostic role of macrophages have documented the relevance of the macrophage population as a whole. However, dissecting the diversity of mononuclear phagocytes in tumor tissues has provided important information about the coexistence of distinct populations of macrophages...
Source: Seminars in Immunology - September 14, 2020 Category: Allergy & Immunology Authors: Cortese N, Carriero R, Laghi L, Mantovani A, Marchesi F Tags: Semin Immunol Source Type: research

NK cells in the tumor microenvironment: Prognostic and theranostic impact. Recent advances and trends.
Abstract NK cells orchestrate the tumor destruction and control metastasis in a coordinated way with other immune cells of the tumor microenvironment. However, NK cell infiltration in the tumor microenvironment is limited, and tumor cells have developed numerous mechanisms to escape NK cell attack. As a result, NK cells that have been able to infiltrate the tumors are exhausted, and metabolically and functionally impaired. Depending this impairment the prognostic and theranostic values of NK cells differ depending on the studies, the type of cancer, the stage of tumor and the nature of the tumor microenvironment. ...
Source: Seminars in Immunology - September 5, 2020 Category: Allergy & Immunology Authors: Russick J, Torset C, Hemery E, Cremer I Tags: Semin Immunol Source Type: research

Introduction to the special issue: Tumor antigens in the time of the coronavirus pandemic.
PMID: 32253110 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - April 3, 2020 Category: Allergy & Immunology Authors: Finn OJ Tags: Semin Immunol Source Type: research

Peptide mimotopes alter T cell function in cancer and autoimmunity.
Abstract T cells recognize and respond to self antigens in both cancer and autoimmunity. One strategy to influence this response is to incorporate amino acid substitutions into these T cell-specific epitopes. This strategy is being reconsidered now with the goal of increasing time to regression with checkpoint blockade therapies in cancer and antigen-specific immunotherapies in autoimmunity. We discuss how these amino acid substitutions change the interactions with the MHC class I or II molecule and the responding T cell repertoire. Amino acid substitutions in epitopes that are the most effective in therapies bind...
Source: Seminars in Immunology - March 20, 2020 Category: Allergy & Immunology Authors: Slansky JE, Nakayama M Tags: Semin Immunol Source Type: research

Tumor antigens in glioma.
Abstract Immunotherapy applications to glioblastoma represent a new treatment frontier. Antigen-targeted immunotherapy approaches hold enormous potential to elicit antigen-specific anti-tumor effects in central nervous system tumors. Still, the paucity of effective antigen targets remains a significant obstacle in safely and effectively treating glioblastoma and other malignant gliomas with relatively low mutation loads. In this review, we highlight the current understanding of and development of immunotherapy to target 1) shared non-mutant antigens 2) shared mutant antigens (neoantigens) derived from cancer-speci...
Source: Seminars in Immunology - February 6, 2020 Category: Allergy & Immunology Authors: Nejo T, Yamamichi A, Almeida ND, Goretsky YE, Okada H Tags: Semin Immunol Source Type: research

Recent advances in tumor associated carbohydrate antigen based chimeric antigen receptor T cells and bispecific antibodies for anti-cancer immunotherapy.
Abstract Tumor associated carbohydrate antigens (TACAs) are a class of attractive antigens for the development of anti-cancer immunotherapy. Besides monoclonal antibodies and vaccines, chimeric antigen receptor (CAR) T cells and bispecific antibodies (BsAbs) targeting TACA are exciting directions to harness the power of the immune system to fight cancer. In this review, we focus on two TACAs, i.e., the GD2 ganglioside and the mucin-1 (MUC1) protein. The latest advances in CAR T cells and bispecific antibodies targeting these two antigens are presented. The roles of co-stimulatory molecules, structures of the seque...
Source: Seminars in Immunology - January 22, 2020 Category: Allergy & Immunology Authors: Rashidijahanabad Z, Huang X Tags: Semin Immunol Source Type: research

Prediction of cancer neoepitopes needs new rules.
Abstract Tumors are immunogenic and the non-synonymous point mutations harbored by tumors are a source of their immunogenicity. Immunologists have long been enamored by the idea of synthetic peptides corresponding to mutated epitopes (neoepitopes) as specific "vaccines" against tumors presenting those neoepitopes in context of MHC I. Tumors may harbor hundreds of point mutations and it would require effective prediction algorithms to identify candidate neoepitopes capable of eliciting potent tumor-specific CD8+ T cell responses. Our current understanding of MHC I-restricted epitopes come from the observa...
Source: Seminars in Immunology - January 14, 2020 Category: Allergy & Immunology Authors: Brennick CA, George MM, Srivastava PK, Karandikar SH Tags: Semin Immunol Source Type: research

MUCIN-4 (MUC4) is a novel tumor antigen in pancreatic cancer immunotherapy.
Abstract Pancreatic cancer (PC) is a highly lethal malignancy with a dismal five-year survival rate. This is due to its asymptomatic nature, lack of reliable biomarkers, poor resectability, early metastasis, and high recurrence rate. Limited efficacies of current treatment modalities treatment-associated toxicity underscore the need for the development of immunotherapy-based approaches. For non-resectable, locally advanced metastatic PC, immunotherapy-based approaches including vaccines, antibody-targeted, immune checkpoint inhibition, CAR-T-cells, and adoptive T-cell transfer could be valuable additions to existi...
Source: Seminars in Immunology - January 14, 2020 Category: Allergy & Immunology Authors: Gautam SK, Kumar S, Dam V, Ghersi D, Jain M, Batra SK Tags: Semin Immunol Source Type: research

Breast cancer stem cell antigens as targets for immunotherapy.
Abstract The great success of immunotherapy is paving the way for a new era in cancer treatment and is driving major improvements in the therapy of patients suffering from a range of solid tumors. However, the choice of the appropriate tumor antigens to be targeted with cancer vaccines and T-cell therapies is still a challenge. Most antigens targeted so far have been identified on the tumor bulk and are expressed on differentiated cancer cells. The discovery of a small population of cancer stem cells (CSC), which is refractory to most current therapies and responsible for the development of metastasis and recurren...
Source: Seminars in Immunology - January 10, 2020 Category: Allergy & Immunology Authors: Quaglino E, Conti L, Cavallo F Tags: Semin Immunol Source Type: research

Post-translational modifications such as citrullination are excellent targets for cancer therapy.
Abstract Under conditions of cellular stress, proteins can be post-translationally modified causing them to be recognized by the immune system. One such stress-induced post-translational modification (siPTM) is citrullination, the conversion of arginine residues to citrulline by peptidylarginine deiminase (PAD) enzymes. PAD enzymes are activated by millimolar concentrations of calcium which can occur during apoptosis, leading to precipitation of proteins, their subsequent uptake by B cells and stimulation of antibody responses. Detection of anti-citrullinated protein antibodies (ACPAs) is a diagnostic of rheumatoi...
Source: Seminars in Immunology - January 10, 2020 Category: Allergy & Immunology Authors: Brentville VA, Vankemmelbeke M, Metheringham RL, Durrant LG Tags: Semin Immunol Source Type: research

Primary immunoprevention of adult onset cancers by vaccinating against retired tissue-specific self-proteins.
Abstract Despite the enormous success of childhood prophylactic vaccination against diseases caused by pathogens, there is currently no similar preventive vaccine program against diseases confronted with age like breast cancer and ovarian cancer. With the exception of the annual influenza vaccine, current recommendations for adult vaccination are for either primary vaccines not received during childhood or for booster vaccinations to maintain the immunity against pathogens already induced during childhood. Here we describe a strategy to provide prophylactic pre-emptive immunity against the development of adult ons...
Source: Seminars in Immunology - January 8, 2020 Category: Allergy & Immunology Authors: Tuohy VK, Johnson JM, Mazumder S Tags: Semin Immunol Source Type: research

Tumor-associated O-glycans of MUC1: Carriers of the glyco-code and targets for cancer vaccine design.
In this report, we will give an overview of the oncogenic functions of MUC1 that are exerted through TACA interactions with endogenous carbohydrate-binding proteins (lectins). These interactions often lead to creation of a pro-tumor microenvironment, favoring tumor progression and metastasis, and tumor evasion. In addition, we will describe current efforts in the design of cancer vaccines with special emphasis on synthetic MUC1 glycopeptide vaccines. Analysis of the key factors that govern structure-based design of immunogenic MUC1 glycopeptide epitopes are described. The role of TACA type, position, and density on observe...
Source: Seminars in Immunology - January 8, 2020 Category: Allergy & Immunology Authors: Beckwith DM, Cudic M Tags: Semin Immunol Source Type: research

Development of autoantibody signatures for common cancers.
Abstract A humoral immune response in the form of autoantibodies to tumor antigens occurs early during tumor development. Identification of antigens that induce an autoantibody response restricted to a cancer type has the potential to yield markers useful for early detection. A multitude of strategies are currently available for the discovery of tumor antigens directed autoantibodies in circulation. Each approach has advantages and limitations for comprehensive discovery of antigenic epitopes. Herein, we review established and novel strategies and methodologies and highlight potential cancer applications. PMI...
Source: Seminars in Immunology - January 7, 2020 Category: Allergy & Immunology Authors: Kobayashi M, Katayama H, Fahrmann JF, Hanash SM Tags: Semin Immunol Source Type: research

Regulation of the complement system and immunological tolerance in pregnancy.
AI Abstract Preeclampsia is a serious vascular complication of the human pregnancy, whose etiology is still poorly understood. In preeclampsia, exacerbated apoptosis and fragmentation of the placental tissue occurs due to developmental qualities of the placental trophoblast cells and/or mechanical and oxidative distress to the syncytiotrophoblast, which lines the placental villi. Dysregulation of the complement system is recognized as one of the mechanisms of the disease pathology. Complement has the ability to promote inflammation and facilitate phagocytosis of placenta-derived particles and apoptotic cells by m...
Source: Seminars in Immunology - November 19, 2019 Category: Allergy & Immunology Authors: Teirilä L, Heikkinen-Eloranta J, Kotimaa J, Meri S, Lokki AI Tags: Semin Immunol Source Type: research

Regulation of regulators: Role of the complement factor H-related proteins.
zsi M Abstract The complement system, while being an essential and very efficient effector component of innate immunity, may cause damage to the host and result in various inflammatory, autoimmune and infectious diseases or cancer, when it is improperly activated or regulated. Factor H is a serum glycoprotein and the main regulator of the activity of the alternative complement pathway. Factor H, together with its splice variant factor H-like protein 1 (FHL-1), inhibits complement activation at the level of the central complement component C3 and beyond. In humans, there are also five factor H-related (FHR) protein...
Source: Seminars in Immunology - November 19, 2019 Category: Allergy & Immunology Authors: Cserhalmi M, Papp A, Brandus B, Uzonyi B, Józsi M Tags: Semin Immunol Source Type: research

The C1q Receptors: Focus on gC1qR/p33 (C1qBP, p32, HABP-1)1.
Abstract In the past several years, a number of C1q binding surface proteins or receptors have been described. This is not of course surprising considering the complexity of the C1q molecule and its ability to bind to a wide range of cellular and plasma proteins via both its collagen-like [cC1q] region and its heterotrimeric globular heads [gC1q] each of which in turn is capable of binding a specific ligand. However, while each of these "receptor" molecules undoubtedly plays a specific function within its restricted microenvironment, and therefore merits full attention, this review nonetheless, will sing...
Source: Seminars in Immunology - November 16, 2019 Category: Allergy & Immunology Authors: Ghebrehiwet B, Geisbrecht BV, Xu X, Savitt AG, Peerschke EIB Tags: Semin Immunol Source Type: research

IL-10 producing regulatory and helper T-cells in systemic lupus erythematosus.
Abstract Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease characterised by the production of pathogenic autoantibodies against nuclear self-antigens. The anti-inflammatory and tolerogenic cytokine Interleukin-10 appears to play a paradoxical pathogenic role in SLE and is therefore currently therapeutically targeted in clinical trials. It is generally assumed that the pathogenic effect of IL-10 in SLE is due to its growth and differentiation factor activity on autoreactive B-cells, but effects on other cells might also play a role. To date, a unique cellular source of pathogenic IL-10...
Source: Seminars in Immunology - November 14, 2019 Category: Allergy & Immunology Authors: Geginat J, Vasco M, Gerosa M, Tas SW, Pagani M, Grassi F, Flavell RA, Meroni P, Abrignani S Tags: Semin Immunol Source Type: research

Immunological biomarkers in severe asthma.
Abstract Severe asthma is heterogeneous in its clinical presentation, underlying pathophysiology, course and response to therapy. Clinical and physiological assessment of severe asthma is often inadequate in predicting underlying disease mechanisms and or response to medications. With the emergence of novel targeted therapies in severe asthma, the need for reproducible, easily measured biomarkers became obvious but only few are currently available for clinical use. These biomarkers along with the clinical presentation of the patient play an important role in identifying phenotypes and endotypes, predicting the cli...
Source: Seminars in Immunology - November 14, 2019 Category: Allergy & Immunology Authors: Narendra D, Blixt J, Hanania NA Tags: Semin Immunol Source Type: research

Immune induction of airway remodeling.
Abstract Airway remodeling is accepted to be a determining component within the natural history of asthma. It is a phenomenon characterized by changes in the airways structures that marches in parallel with and can be influenced by airway inflammation, floating at the interface between both natural and adaptive immunity and physical and mechanical cells behavior. In this review we aimed to highlight the comprehensive, yet not exhaustive, evidences of how immune cells induce, regulate and adapt to the recognized markers of airway remodeling. Mucous cell hyperplasia, epithelial dysfunction and mesenchymal transition...
Source: Seminars in Immunology - November 14, 2019 Category: Allergy & Immunology Authors: Guida G, Riccio AM Tags: Semin Immunol Source Type: research

Title: IL-10-producing T cells and their dual functions.
Abstract Interleukin (IL)-10 is considered a prototypical anti-inflammatory cytokine, which significantly contributes to the maintenance and reestablishment of immune homeostasis. However, this classical view fails to fully describe the pleiotropic roles of IL-10. Indeed, IL-10 can also promote immune responses, e.g. by supporting B-cell and CD8+ T-cell activation. The reasons for these seemingly opposing functions are unclear to a large extent. Recent and previous studies suggest that the cellular source and the microenvironment impact the function of IL-10. However, studies addressing the mechanisms which determ...
Source: Seminars in Immunology - November 14, 2019 Category: Allergy & Immunology Authors: Bedke T, Muscate F, Soukou S, Gagliani N, Huber S Tags: Semin Immunol Source Type: research

Properties and functions of the novel type i interferon epsilon.
PROPERTIES AND FUNCTIONS OF THE NOVEL TYPE I INTERFERON EPSILON. Semin Immunol. 2019 Nov 14;:101328 Authors: Marks ZRC, Campbell N, deWeerd NA, Lim SS, Gearing LJ, Bourke NM, Hertzog PJ Abstract Interferon epsilon (IFNε) is a type I IFN with unusual patterns of expression and therefore, function. It is constitutively expressed by reproductive tract epithelium and regulated by hormones during estrus cycle, reproduction, and menopause and by exogenous hormones. The IFNe protein is encoded by a gene in the type I IFN locus, binds to IFNAR1 and 2 which are required for signaling via the JAK STAT p...
Source: Seminars in Immunology - November 14, 2019 Category: Allergy & Immunology Authors: Marks ZRC, Campbell N, deWeerd NA, Lim SS, Gearing LJ, Bourke NM, Hertzog PJ Tags: Semin Immunol Source Type: research

Editorial to the ASTHMA Issue.
PMID: 31734131 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - November 13, 2019 Category: Allergy & Immunology Authors: Canonica GW Tags: Semin Immunol Source Type: research

Disturbances in complement recognition and control in human disease.
PMID: 31734132 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - November 13, 2019 Category: Allergy & Immunology Authors: Meri S Tags: Semin Immunol Source Type: research

Functions and regulation of T cell-derived interleukin-10.
Abstract Interleukin (IL)-10 is an essential anti-inflammatory cytokine and functions as a negative regulator of immune responses to microbial antigens. IL-10 is particularly important in maintaining the intestinal microbe-immune homeostasis. Loss of IL-10 promotes the development of inflammatory bowel disease (IBD) as a consequence of an excessive immune response to the gut microbiota. IL-10 also functions more generally to prevent excessive inflammation during the course of infection. Although IL-10 can be produced by virtually all cells of the innate and adaptive immune system, T cells constitute a non-redundan...
Source: Seminars in Immunology - November 11, 2019 Category: Allergy & Immunology Authors: Neumann C, Scheffold A, Rutz S Tags: Semin Immunol Source Type: research

Complement activation and regulation in rheumatic disease.
Abstract Complement is a key component of the innate immune defence and in addition forms a bridge to the adaptive immune responses. As such complement is of vital importance for efficient protection against infections. However, the activity of the complement system can also aberrantly be directed against the tissues of the body itself and contribute to organ damage in a variety of diseases. In several rheumatic diseases complement activation is suggested to play a pronounced role. This review will highlight the role of both complement activation and complement regulation in rheumatic disease. A contribution of co...
Source: Seminars in Immunology - November 9, 2019 Category: Allergy & Immunology Authors: Dijkstra DJ, Joeloemsingh JV, Bajema IM, Trouw LA Tags: Semin Immunol Source Type: research

Complement dysregulation in glomerulonephritis.
Abstract Glomerulonephritis (GN) refers to a group of renal diseases affecting the glomeruli due to the damage mediated by immunological mechanisms. A large proportion of the disease manifestations are caused by disturbances in the complement system. They can be due to genetic errors, autoimmunity, microbes or abnormal immunoglobulins, like modified IgA or paraproteins. The common denominator in most of the problems is an overactive or misdirected alternative pathway complement activation. An assessment of kidney function, amount of proteinuria and hematuria are crucial elements to evaluate, when glomerulonephriti...
Source: Seminars in Immunology - November 8, 2019 Category: Allergy & Immunology Authors: Kaartinen K, Safa A, Kotha S, Ratti G, Meri S Tags: Semin Immunol Source Type: research

Il-10 producing T and B cells in allergy.
Abstract The molecular and cellular mechanisms of allergen tolerance in humans have been intensively studied in the past few decades. The demonstration of epitope-specific T cell tolerance, particularly mediated by the immune suppressor functions of IL-10 led to a major conceptual change in this area more than 20 years ago. Currently, the known essential components of allergen tolerance include the induction of allergen-specific regulatory of T and B cells, the immune suppressive function of secreted factors, such as IL-10, IL-35, IL-1 receptor antagonist and TGF-β, immune suppressive functions of surface mol...
Source: Seminars in Immunology - November 8, 2019 Category: Allergy & Immunology Authors: Boonpiyathad T, Satitsuksanoa P, Akdis M, Akdis CA Tags: Semin Immunol Source Type: research

Allergen immunotherapy (AIT) in asthma.
Abstract Bronchial asthma remains one of the most common chronic diseases with a high degree of morbidity and still a considerable mortality with an increasing prevalence in many countries. Although remarkable progress has been made in the past decades in the medical treatment for asthma, curative or disease modifying approaches are still limited to allergen immunotherapy (AIT). Despite a plethora of potential immunological actions observed during AIT, the precise mechamisms that might exert beneficial effects especially in asthma remain unclear. Clinical studies in the past have suggested clinical benefits in sym...
Source: Seminars in Immunology - November 8, 2019 Category: Allergy & Immunology Authors: Virchow JC Tags: Semin Immunol Source Type: research

Complement dysregulation in the central nervous system during development and disease.
Abstract The complement cascade is an important arm of the immune system that plays a key role in protecting the central nervous system (CNS) from infection. Recently, it has also become clear that complement proteins have fundamental roles in the developing and aging CNS that are distinct from their roles in immunity. During neurodevelopment, complement signalling is involved in diverse processes including neural tube closure, neural progenitor proliferation and differentiation, neuronal migration, and synaptic pruning. In acute neurotrauma and ischamic brain injury, complement drives inflammation and neuronal de...
Source: Seminars in Immunology - November 7, 2019 Category: Allergy & Immunology Authors: Lee JD, Coulthard LG, Woodruff TM Tags: Semin Immunol Source Type: research

Immune regulation and cytotoxic T cell activation of IL-10 agonists - Preclinical and clinical experience.
Abstract The expansion and activation of tumor antigen reactive CD8+ T cells are primary goals of immunotherapies for cancer. IL-10 is an anti-inflammatory cytokine with an essential role in the development and proliferation of regulatory T cells, restricting myeloid and chronic inflammatory T cell responses. However, IL-10 is also essential for the expansion of antigen activated, tumor specific CD8+ T cells, leading to spontaneous tumor development in IL-10 deficient patients and mice. IL-10 induces IFNγ and cytotoxic mediators in antigen activated T cells. In clinical trials, monotherapy with recombinant, ...
Source: Seminars in Immunology - November 6, 2019 Category: Allergy & Immunology Authors: Oft M Tags: Semin Immunol Source Type: research

Introduction to the Special Issue: Interleukin-10.
PMID: 31706854 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - November 6, 2019 Category: Allergy & Immunology Authors: Geginat J Tags: Semin Immunol Source Type: research

Immunologic mechanisms in asthma.
CA Abstract Asthma is a chronic airway disease, which affects more than 300 million people. The pathogenesis of asthma exhibits marked heterogeneity with many phenotypes defining visible characteristics and endotypes defining molecular mechanisms. With the evolution of novel biological therapies, patients, who do not-respond to conventional asthma therapy require novel biologic medications, such as anti-IgE, anti-IL-5 and anti-IL4/IL13 to control asthma symptoms. It is increasingly important for physicians to understand immunopathology of asthma and to characterize asthma phenotypes. Asthma is associated with imm...
Source: Seminars in Immunology - November 5, 2019 Category: Allergy & Immunology Authors: Boonpiyathad T, Sözener ZC, Satitsuksanoa P, Akdis CA Tags: Semin Immunol Source Type: research

Disturbances in complement recognition and control in human disease - An editorial to a special issue on "Complement Regulation".
Disturbances in complement recognition and control in human disease - An editorial to a special issue on "Complement Regulation". Semin Immunol. 2019 Nov 05;:101345 Authors: Meri S PMID: 31703833 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - November 5, 2019 Category: Allergy & Immunology Authors: Meri S Tags: Semin Immunol Source Type: research

IL-10-producing regulatory B cells and plasmocytes: Molecular mechanisms and disease relevance.
Abstract It has long been assumed that the functions of B cells reflected the roles of antibodies. However, B cells also decisively influence immunity via antibody-independent mechanisms including the presentation of antigen to T cells and the secretion of cytokines. In fact, B cell depletion therapy improves the course of autoimmune diseases such as multiple sclerosis by removing pro-inflammatory cytokine-producing B cells rather than by reducing autoantibody levels. Remarkably, B cells can also produce anti-inflammatory cytokines, and subsequently suppress immunity, providing protection from autoimmune diseases ...
Source: Seminars in Immunology - November 1, 2019 Category: Allergy & Immunology Authors: Cerqueira C, Manfroi B, Fillatreau S Tags: Semin Immunol Source Type: research

Epigenetic and transcriptional mechanisms for the regulation of IL-10.
Abstract IL-10 is a critical immunoregulatory cytokine expressed in virtually all immune cell types. Maintaining a delicate balance between effective immune response and tolerance requires meticulous and dynamic control of IL-10 expression both epigenetically and transcriptionally. In this Review, we describe the epigenetic mechanisms controlling IL-10 expression, including chromatin remodeling, 3D chromatin loops, histone modification and DNA methylation. We discuss the role of transcription factors in directing chromatin modifications, with a special highlight on the emerging concept of pioneer transcription fac...
Source: Seminars in Immunology - October 29, 2019 Category: Allergy & Immunology Authors: Zhang H, Kuchroo V Tags: Semin Immunol Source Type: research

Introduction to special issue on interferons.
PMID: 31668551 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - October 23, 2019 Category: Allergy & Immunology Authors: Fish E Tags: Semin Immunol Source Type: research

Interleukin-10 mediated immune regulation after stem cell transplantation: Mechanisms and implications for therapeutic intervention.
Abstract Interleukin-10 (IL-10) is a multi-faceted anti-inflammatory cytokine which plays an essential role in immune tolerance. Indeed, deficiency of IL-10 or its receptor results in aberrant immune responses that lead to immunopathology. Graft-versus-host disease (GVHD) is the limiting complication of allogeneic stem cell transplantation (SCT) and results from an imbalance in pathological versus regulatory immune networks. A number of immune cells exert their immunomodulatory role through secretion of IL-10 or induction of IL-10-secreting cells after SCT. Type-1 regulatory T cells (Tr1 cells) and FoxP3+ regulato...
Source: Seminars in Immunology - October 19, 2019 Category: Allergy & Immunology Authors: Zhang P, Hill GR Tags: Semin Immunol Source Type: research

Innate lymphoid cells and cancer at border surfaces with the environment.
Abstract Innate lymphoid cells (ILC) are a recently identified group of innate lymphocytes. ILC are subdivided into cytotoxic ILC (i.e., conventional natural killer (NK) cells) and helper ILC. Helper ILC are tissue-resident cells that have been involved in various physiological and pathological processes of organs and tissues. While their roles during inflammation are well studied, their contribution to tumor immunity is not well known. Here, we will provide an overview of the various helper ILC subsets, their development and function and discuss their potential roles during tumorigenesis and for anti-tumor immuni...
Source: Seminars in Immunology - August 28, 2019 Category: Allergy & Immunology Authors: Mattiola I, Diefenbach A Tags: Semin Immunol Source Type: research

Severe asthma phenotypes and endotypes.
Abstract Current management of severe asthma relying either on guidelines (bulk approach) or on disease phenotypes (stratified approach) did not improve the burden of the disease. Several severe phenotypes are described: clinical, functional, morphological, inflammatory, molecular and microbiome-related. However, phenotypes do not necessarily relate to or give insights into the underlying pathogenetic mechanisms which are described by the disease endotypes. Based on the major immune-inflammatory pathway involved type-2 high, type-2 low and mixed endotypes are described for severe asthma, with several shared pathog...
Source: Seminars in Immunology - August 27, 2019 Category: Allergy & Immunology Authors: Agache I Tags: Semin Immunol Source Type: research

Asthma from immune pathogenesis to precision medicine.
Abstract Asthma is characterized by multiple immunological mechanisms (endotypes) determining variable clinical presentations (phenotypes). The identification of endotypic mechanisms is crucial to better characterize patients and to identify tailored therapeutic approaches with novel biological agents targeting specific immunological pathways. This review focused on summarizing the major immunological mechanisms involved in the pathogenesis of asthma, as well as on discussing the emergence of phenotypic features of the disease. Novel biological agents and other drugs targeting specific endotypes are discussed, as ...
Source: Seminars in Immunology - August 3, 2019 Category: Allergy & Immunology Authors: Khalaf K, Paoletti G, Puggioni F, Racca F, De Luca F, Giorgis V, Canonica GW, Heffler E Tags: Semin Immunol Source Type: research

ILC regulation of T cell responses in inflammatory diseases and cancer.
Abstract The tumor microenvironment is shaped by interactions between tumor cells, stroma, and immune cells. T cells are a critical component of the immunological anti-tumor response and most immunotherapeutic approaches in cancer aim to augment T cell responses. Recently, innate lymphoid cells (ILCs) have been added to the list of cell populations that influence T cell responses within the tumor microenvironment. ILCs were shown to modulate T cell functions through a variety of mechanisms. However, the impact of ILC and T cell interactions on disease outcome appears to be contextual as their phenotype and functio...
Source: Seminars in Immunology - August 2, 2019 Category: Allergy & Immunology Authors: Warner K, Ohashi PS Tags: Semin Immunol Source Type: research

To be a tumor promoting or tumor suppressing ILC: That is the question.
PMID: 31337579 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - July 20, 2019 Category: Allergy & Immunology Authors: Jandus C Tags: Semin Immunol Source Type: research

IFN- γ: A cytokine at the right time, is in the right place.
IFN-γ: A cytokine at the right time, is in the right place. Semin Immunol. 2019 Jun 17;:101280 Authors: Burke JD, Young HA Abstract Interferon gamma has long been studied as a critical mediator of tumor immunity. In recent years, the complexity of cellular interactions that take place in the tumor microenvironment has become better appreciated in the context of immunotherapy. While checkpoint inhibitors have dramatically improved remission rates in cancer treatment, IFN-γ and related effectors continue to be identified as strong predictors of treatment success. In this review, we provide a...
Source: Seminars in Immunology - June 17, 2019 Category: Allergy & Immunology Authors: Burke JD, Young HA Tags: Semin Immunol Source Type: research

ILCs in hematologic malignancies: Tumor cell killers and tissue healers.
Abstract Innate lymphoid cells (ILCs) have attracted considerable attention in the past years. As modulators of epithelial barrier immunology and homeostasis they play important roles in (auto)immunity and inflammation. Here we review the role of ILCs in hematologic malignancies, where ILCs act as efficient killer cells and as tissue healers, in the context of chemotherapy, radiotherapy and after allogeneic hematopoietic stem cell transplantation (HSCT). PMID: 31200953 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - June 11, 2019 Category: Allergy & Immunology Authors: Blom B, van Hoeven V, Hazenberg MD Tags: Semin Immunol Source Type: research

Type I interferon signaling, regulation and gene stimulation in chronic virus infection.
Abstract Type I Interferons (IFN-I) mediate numerous immune interactions during viral infections, from the establishment of an antiviral state to invoking and regulating innate and adaptive immune cells that eliminate infection. While continuous IFN-I signaling plays critical roles in limiting virus replication during both acute and chronic infections, sustained IFN-I signaling also leads to chronic immune activation, inflammation and, consequently, immune exhaustion and dysfunction. Thus, an understanding of the balance between the desirable and deleterious effects of chronic IFN-I signaling will inform our quest...
Source: Seminars in Immunology - May 30, 2019 Category: Allergy & Immunology Authors: Lukhele S, Boukhaled GM, Brooks DG Tags: Semin Immunol Source Type: research

The pro- and anti-tumor role of ILC2s.
dus C Abstract Group 2 innate lymphoid cells (ILC2s) are critical for the initiation of type 2 inflammatory diseases. However, ILC2s are also involved in the establishment of the immune microenvironment during tumor development, growth and metastasization. In this context, ILC2s have been shown to be either tumor-suppressive or tumor-promoting according to the tumor type, the cytokine secreted and the other immune cells that are, in turn, recruited and/or activated. PMID: 31130471 [PubMed - as supplied by publisher] (Source: Seminars in Immunology)
Source: Seminars in Immunology - May 23, 2019 Category: Allergy & Immunology Authors: Trabanelli S, Chevalier MF, Derré L, Jandus C Tags: Semin Immunol Source Type: research

Senescent cell clearance by the immune system: Emerging therapeutic opportunities.
Abstract Senescent cells (SCs) arise from normal cells in multiple organs due to inflammatory, metabolic, DNA damage, or tissue damage signals. SCs are non-proliferating but metabolically active cells that can secrete a range of pro-inflammatory and proteolytic factors as part of the senescence-associated secretory phenotype (SASP). Senescent cell anti-apoptotic pathways (SCAPs) protect SCs from their own pro-apoptotic SASP. SCs can chemo-attract immune cells and are usually cleared by these immune cells. During aging and in multiple chronic diseases, SCs can accumulate in dysfunctional tissues. SCs can impede inn...
Source: Seminars in Immunology - May 11, 2019 Category: Allergy & Immunology Authors: Prata LGPL, Ovsyannikova IG, Tchkonia T, Kirkland JL Tags: Semin Immunol Source Type: research

NK cells to cure cancer.
Abstract Natural Killer (NK) cells are innate lymphocytes able to mediate immune-surveillance and clearance of viral infected and tumor-transformed cells. Growing experimental and clinical evidence highlighted a dual role of NK cells either in the control of cancer development/progression or in promoting the onset of immune-suppressant tumor microenvironments. Indeed, several mechanisms of NK cell-mediated tumor escape have been described and these includes cancer-induced aberrant expression of activating and inhibitory receptors (i.e. NK cell immune checkpoints), impairments of NK cell migration to tumor sites an...
Source: Seminars in Immunology - May 10, 2019 Category: Allergy & Immunology Authors: Di Vito C, Mikulak J, Zaghi E, Pesce S, Marcenaro E, Mavilio D Tags: Semin Immunol Source Type: research

Helper-like innate lymphoid cells and cancer immunotherapy.
;ry M Abstract Immunotherapies have revolutionized cancer treatment over the last 20 years. They aim either to boost immune cell activation or decrease immune cell inhibition, to improve control over cancer development. Various strategies for improving tumor immunity have been tested. Some have been approved and others are currently in clinical trials. They target the immune system itself, the tumor cells or the microenvironment. Most focus on enhancing T-cell responses, notably through infusions of activating cytokines, the adoptive transfer of activated or engineered T cells, or immune checkpoint inhibitors. ILC...
Source: Seminars in Immunology - May 6, 2019 Category: Allergy & Immunology Authors: Crinier A, Vivier E, Bléry M Tags: Semin Immunol Source Type: research