Oral and sublingual immunotherapy for food allergy: current progress and future directions.
Abstract Food allergies are increasing in prevalence and present an emerging epidemic for westernized countries. Strict dietary avoidance is the only approved management for food allergy, but accidental exposures regularly occur, leading to significant patient anxiety and decreased quality of life. Over the past decade, oral and sublingual immunotherapies have emerged as potential treatments for food allergy. While several small clinical trials have demonstrated that immunotherapy can desensitize food-allergic individuals, strategies for further enhancing safety and definitively establishing long-term efficacy are...
Source: Current Opinion in Immunology - August 20, 2013 Category: Allergy & Immunology Authors: Moran TP, Vickery BP, Burks AW Tags: Curr Opin Immunol Source Type: research

Immune senescence: new insights into defects but continued mystery of root causes.
PMID: 23962425 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - August 17, 2013 Category: Allergy & Immunology Authors: Swain SL, Blomberg BB Tags: Curr Opin Immunol Source Type: research

Variability in the immune system: of vaccine responses and immune states.
Abstract System-wide approaches are now being applied to study vaccine responses, whose mechanisms of action, and failure, are not well understood. These works have repeatedly shown vaccine response to be an orchestrated process involving multiple arms of immunity most noticeable sensing and innate components. Prediction of vaccine responses based on system-wide measures is achievable, but challenges remain for robust population wide predictions based only on pre-vaccination measures, especially in partially efficacious vaccines such as influenza. This is especially true in older adults, who are often less respons...
Source: Current Opinion in Immunology - August 13, 2013 Category: Allergy & Immunology Authors: Shen-Orr SS, Furman D Tags: Curr Opin Immunol Source Type: research

Correlates of protection against influenza infection in humans-on the path to a universal vaccine?
Abstract Influenza is an acute respiratory viral infection with high mutation rate and pandemic potential. Vaccination is an effective means of prevention and control of influenza, but the challenges of vaccine mismatches for the next influenza seasons and adequate global supply of influenza vaccines limit its effectiveness. Protective immunity in vaccination or natural infection is primarily mediated by antibody responses against surface proteins of influenza including haemagglutinin (HA) as the major neutralizing target, whereas strong T cell responses to internal viral proteins are associated with reduced disea...
Source: Current Opinion in Immunology - August 12, 2013 Category: Allergy & Immunology Authors: Li CK, Rappuoli R, Xu XN Tags: Curr Opin Immunol Source Type: research

A comparative review of aging and B cell function in mice and humans.
Abstract Immune system function declines with age. Here we review and compare age-associated changes in murine and human B cell pools and humoral immune responses. We summarize changes in B cell generation and homeostasis, as well as notable changes at the subcellular level; then discuss how these changes help to explain alterations in immune responses across the adult lifespan of the animal. In each section we compare and contrast findings in the mouse, arguably the best animal model of the aging immune system, with current understanding of B cell immunity in humans. PMID: 23932400 [PubMed - as supplied by p...
Source: Current Opinion in Immunology - August 6, 2013 Category: Allergy & Immunology Authors: Scholz JL, Diaz A, Riley RL, Cancro MP, Frasca D Tags: Curr Opin Immunol Source Type: research

Host-pathogen interaction in HIV infection.
Abstract The host-pathogen interaction is strikingly complex during HIV infection. While several immune effector mechanisms (i.e. cytotoxic T cells, neutralizing antibodies, NK cells, among others) can play a strong antiviral role in vivo, the virus is remarkably able to evade these responses. In addition, the virus preferentially infects and kills activated memory CD4+ T cells, thus exploiting the host antiviral immune response as a source of new cellular targets for infection. Recent advances in understanding (i) how HIV perturbs the host immune system, (ii) how the immune system fights HIV; and (iii) how HIV di...
Source: Current Opinion in Immunology - July 24, 2013 Category: Allergy & Immunology Authors: Chowdhury A, Silvestri G Tags: Curr Opin Immunol Source Type: research

Comparative immunology: allorecognition and variable surface receptors outside the jawed vertebrates.
Abstract Allograft rejection is one of several undesirable consequences of the adaptive nature of the mammalian immune response. This review examines adaptive immune responses and allorecognition in animals with very different immune responses - jawless vertebrates, arthropods, and two distinct colonial marine invertebrates - with the goal of understanding how immune adaptation and allograft rejection are linked, and conversely how a system works where allograft rejection is a desired outcome rather than an unforeseen consequence. PMID: 23890586 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - July 24, 2013 Category: Allergy & Immunology Authors: Dionne MS Tags: Curr Opin Immunol Source Type: research

Specificity, promiscuity, and precursor frequency in immunoreceptors.
Abstract The immune system is comprised of various immune cell populations that utilize a spectrum of immunoreceptors characterized by different levels of specificity, diversity, and prevalence within a host and across a population. These range from the universal receptors employed by both innate cells and innate-like cells, such as NKT and MAIT cells, through to receptors expressed on T cells with sporadic incidence. Here we review recent advances in understanding the molecular mechanisms that drive the observed spectra of T cell receptors in vivo. PMID: 23880376 [PubMed - as supplied by publisher] (Source: ...
Source: Current Opinion in Immunology - July 20, 2013 Category: Allergy & Immunology Authors: Venturi V, Rudd BD, Davenport MP Tags: Curr Opin Immunol Source Type: research

Thymic rejuvenation and aging.
Abstract The thymus is a vital organ for homeostatic maintenance of the peripheral immune system. It is within this mediastinal tissue that T cells develop and are extensively educated and exported to the periphery for establishment of a functional and effective immune system. A striking paradoxical feature of this critical lymphoid tissue is that it undergoes profound age-associated involution. Thymic decline is of minimal consequence to healthy individuals, but the reduced efficacy of the immune system with age has direct etiological linkages with an increase in diseases including opportunistic infections, autoi...
Source: Current Opinion in Immunology - July 4, 2013 Category: Allergy & Immunology Authors: Ventevogel MS, Sempowski GD Tags: Curr Opin Immunol Source Type: research

Resident commensals shaping immunity.
Abstract All animals coexist with myriad commensal microorganisms in a symbiotic relationship that plays a key role in health and disease. Continuous commensal-host interactions profoundly affect the development and regulation of the host's immune system. The complex interaction of the commensal microbiota with the immune system is a topic of substantial interest. An understanding of these interactions and the mechanisms through which commensal microbes actively shape host immunity may yield new insights into the pathogenesis of many immune-mediated diseases and lead to new prophylactic and therapeutic interventio...
Source: Current Opinion in Immunology - July 2, 2013 Category: Allergy & Immunology Authors: Erturk-Hasdemir D, Kasper DL Tags: Curr Opin Immunol Source Type: research

Immunosenescence: a product of the environment?
Abstract The major function of the immune system is to provide protection against pathogens, in order to prevent infections and potential death. However, with increasing age the immune system undergoes alterations culminating in a progressive deterioration in the ability to respond to infection and vaccination. The precise mechanisms associated with immunosenescence have not been fully elucidated although extensive analyses have suggested that intrinsic defects within immune cells are potentially involved. Despite the stromal niche playing a critical role in the development and activation of immune cells, the role...
Source: Current Opinion in Immunology - June 25, 2013 Category: Allergy & Immunology Authors: Su DM, Aw D, Palmer DB Tags: Curr Opin Immunol Source Type: research

Impact of aging on antigen presentation cell function of dendritic cells.
Abstract Older people exhibit increased mortality to infections and cancer as compared to younger people, indicating that aging impairs immunity. Dendritic cells (DCs) are key for bridging the innate and adaptive arms of the immune system by priming antigen specific T cells. Discerning how aging impacts DC function to initiate adaptive immune responses is of great biomedical importance as this could lead to the development of novel therapeutics to enhance immunity with aging. This review details reports indicating that aging impairs the antigen presenting function of DCs but highlights other studies indicating pre...
Source: Current Opinion in Immunology - June 24, 2013 Category: Allergy & Immunology Authors: Wong C, Goldstein DR Tags: Curr Opin Immunol Source Type: research

Masters, marionettes and modulators: intersection of pathogen virulence factors and mammalian death receptor signaling.
Abstract TNF and its receptor, TNFR1, are members of the TNF superfamily and play important roles during infection by orchestrating an inflammatory response. The key role that TNFR1 signaling plays in host defense singles it out as a frequent target of pathogen manipulation. This review describes how the TNFR1 signaling pathway is attacked by pathogen virulence factors and how the different TNFR1 signaling pathways, in particular the death signaling response, have evolved to counteract these pathogen manipulations. We examine recent data showing that other 'Death Receptors' in the TNF superfamily, namely TRAIL-R a...
Source: Current Opinion in Immunology - June 22, 2013 Category: Allergy & Immunology Authors: Silke J, Hartland EL Tags: Curr Opin Immunol Source Type: research

Host pathogen interactions at the coalface of immunity.
PMID: 23790534 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - June 19, 2013 Category: Allergy & Immunology Authors: Pellegrini M, Walker BD Tags: Curr Opin Immunol Source Type: research

Counterpoise between the microbiome, host immune activation and pathology.
Abstract The role of the mammalian intestinal microbiota in health and disease of the host has long been recognized and extensively studied. Largely, these studies have focused on the bacterial component of the microbiota. However, recent technological advances have shed new light on the microbiome at distinct anatomical locations and uncovered the role of additional microbial symbionts, including the virome and endogenous retroelements. Together, they have revealed interactions more intricate than previously recognized. Here, we review recent advances in our knowledge of this collective microbiome and the interac...
Source: Current Opinion in Immunology - June 3, 2013 Category: Allergy & Immunology Authors: Mavrommatis B, Young GR, Kassiotis G Tags: Curr Opin Immunol Source Type: research

New effector functions and regulatory mechanisms of BCL6 in normal and malignant lymphocytes.
Abstract The BCL6 oncogenic repressor is a master regulator of humoral immunity and B-cell lymphoma survival. Whereas much research has focused on its regulation and function in germinal center B-cells, its role in other mature lymphoid cell compartments is less clear. A novel role for BCL6 in follicular T helper cell development was recently uncovered. The latest discoveries reveal that BCL6 is also an important regulator of other specialized helper T-cell subsets within germinal centers, pre-germinal center events, and peripheral T-cell effector functions. Here, we review newly discovered roles for BCL6 in lymph...
Source: Current Opinion in Immunology - May 29, 2013 Category: Allergy & Immunology Authors: Bunting KL, Melnick AM Tags: Curr Opin Immunol Source Type: research

Human dendritic cell subsets in vaccination.
Abstract Owing to their properties, dendritic cells (DCs) are often called 'nature's adjuvants' and thus have become the natural targets for antigen delivery. DCs provide an essential link between the innate and the adaptive immune responses. DCs are at the center of the immune system owing to their ability to control both tolerance and immunity. DCs are thus key targets for both preventive and therapeutic vaccination. Herein, we will discuss recent progresses in our understanding of DC subsets physiology as it applies to vaccination. PMID: 23725656 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - May 29, 2013 Category: Allergy & Immunology Authors: Palucka K, Banchereau J Tags: Curr Opin Immunol Source Type: research

Monitoring the immune response in sepsis: a rational approach to administration of immunoadjuvant therapies.
Abstract Preliminary studies suggest that a subgroup of septic patients with severe immune alterations is at high risk of death or nosocomial infection and therefore could benefit from adjunctive immune stimulating therapies. There is thus an urgent need for robust biomarkers usable in routine conditions evaluating rapidly evolving immune status in patients. Although functional testing remains a gold standard, its standardization remains challenging. Therefore, surrogate markers such as monocyte HLA-DR expression, are being developed. Such biomarkers of immune functionality will enable a novel approach in the desi...
Source: Current Opinion in Immunology - May 28, 2013 Category: Allergy & Immunology Authors: Venet F, Lukaszewicz AC, Payen D, Hotchkiss R, Monneret G Tags: Curr Opin Immunol Source Type: research

Multiple players in mouse B cell memory.
Abstract B cell memory has long been considered the attribute of the sole IgG-positive B cell subset. Since a few years, and due to new B-cell subset identification procedures, increasing heterogeneity has been identified among the memory B cell pool. IgM-positive cells and germinal center-independent subsets are recent additions to the field. This review describes the diversity of memory B cells, as well as controversial issues on their relative contribution to the recall response. The impact of a protracted germinal center response to the specific mobilization of IgM memory B cells is proposed. PMID: 237258...
Source: Current Opinion in Immunology - May 28, 2013 Category: Allergy & Immunology Authors: Weill JC, Le Gallou S, Hao Y, Reynaud CA Tags: Curr Opin Immunol Source Type: research

Inflammation in tuberculosis: interactions, imbalances and interventions.
Abstract Inflammation is critical for tuberculosis (TB) pathogenesis. The nonresolving aspect of inflammation in TB is caused by sophisticated intracellular survival strategies of tubercle bacilli. TB is a continuum comprising a spectrum of lesions as a consequence of complex regulation of inflammation. Proinflammatory cytokines, including interferons, tumor necrosis factor and interleukin 1 along with microRNAs and eicosanoids form an interactive network during TB. Cross-regulation between proinflammatory mediators strongly impacts on infected cell death patterns. These processes, in concert with local concentrat...
Source: Current Opinion in Immunology - May 28, 2013 Category: Allergy & Immunology Authors: Kaufmann SH, Dorhoi A Tags: Curr Opin Immunol Source Type: research

mTOR and lymphocyte metabolism.
Abstract Upon antigen engagement and proper co-stimulation, naïve lymphocytes exit quiescence and undergo clonal expansion and differentiate into functional effector cells, after which they either die through apoptosis or survive as memory cells. Lymphocytes at different activation stages exhibit distinct metabolic signatures. Emerging evidence highlights a central role for the mechanistic target of rapamycin (mTOR) in bridging immune signals and metabolic cues to direct lymphocyte proliferation, differentiation and survival. Here we review recent advances in understanding the functional significance and sign...
Source: Current Opinion in Immunology - May 27, 2013 Category: Allergy & Immunology Authors: Zeng H, Chi H Tags: Curr Opin Immunol Source Type: research

Vaccines.
PMID: 23714601 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - May 25, 2013 Category: Allergy & Immunology Authors: Caminschi I, Lew AM Tags: Curr Opin Immunol Source Type: research

Dynamic regulation of Bcl6 in follicular helper CD4 T (Tfh) cells.
Abstract Our bodies are continuously exposed to various types of infectious pathogens. Vaccinations are the most cost effective way to protect our bodies against a variety of infectious microbes. The efficacy of most vaccines relies on protective antibody production and generation of memory B cells. These two key components develop mostly from B cells that participate in germinal center reactions. Recent efforts have highlighted the critical role of follicular helper CD4 T (Tfh) cells in the generation of germinal centers. Given that Bcl6 is a major transcription factor for Tfh differentiation, here we review rece...
Source: Current Opinion in Immunology - May 17, 2013 Category: Allergy & Immunology Authors: Choi YS, Yang JA, Crotty S Tags: Curr Opin Immunol Source Type: research

Phosphatase regulation of immunoreceptor signaling in T cells, B cells and mast cells.
n M Abstract Recent progress has begun to reveal the often complex and changing roles of phosphotyrosine and phosphoinositide phosphatases in regulation of immunoreceptor signaling. The resultant confusion has been further increased by discoveries of new players. Here we provide a review of recent progress in defining the roles of these enzymes in immunoreceptor-dependent mast cell, T cell and B cell activation. PMID: 23684445 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - May 15, 2013 Category: Allergy & Immunology Authors: Bounab Y, Getahun A, Cambier JC, Daëron M Tags: Curr Opin Immunol Source Type: research

Th17 cell based vaccines in mucosal immunity.
Abstract Vaccination is proven to be effective in controlling many infections including small pox, influenza and hepatitis, but strain-specific factors may limit vaccine efficacy. All of these vaccines work through the generation of neutralizing antibodies but for some pathogens there may be roles for serotype-independent immunity. Recently several groups using murine vaccine models have shown that induced T helper cell responses including Th17 responses have shown the potential for CD4+ T-cell dependent vaccine responses. Th17 mediated protective responses involve the recruitment of neutrophils, release of anti-m...
Source: Current Opinion in Immunology - May 10, 2013 Category: Allergy & Immunology Authors: Kumar P, Chen K, Kolls JK Tags: Curr Opin Immunol Source Type: research

Human immune responses and potential for vaccine assessment in humanized mice.
Abstract The new humanized mouse models with a transplanted human immune system have a capacity for de novo multilineage human hematopoiesis and generate T cells, B cells, macrophages, dendritic cells and NK cells. Of the two current leading humanized mouse models, the hu-HSC model is created by human hematopoietic stem cell (HSC) engraftment whereas the BLT mouse model is prepared by co-transplantation of human fetal liver, thymus and HSC. Humoral and cellular immune responses are seen in both models after immunization with antigens or infection with hematotropic pathogens such as EBV, HIV-1 and dengue viruses. W...
Source: Current Opinion in Immunology - April 26, 2013 Category: Allergy & Immunology Authors: Akkina R Tags: Curr Opin Immunol Source Type: research

Controversy and consensus regarding myosin II function at the immunological synapse.
Abstract Regulated actin dynamics play a central role in modulating signaling events at the immunological synapse (IS). Polymerization of actin filaments at the periphery of the IS, coupled to depolymerization near the center, generates a centripetal flow of the actin network and associated movement of signaling molecules. A recent flurry of papers addresses the role of myosin II in facilitating these events. Investigators agree that myosin II is present at the IS, where it forms actomyosin arcs within the peripheral supramolecular activation cluster, a region corresponding to the lamellum of migrating cells. Howe...
Source: Current Opinion in Immunology - April 24, 2013 Category: Allergy & Immunology Authors: Hammer JA, Burkhardt JK Tags: Curr Opin Immunol Source Type: research

Manipulating the PD-1 pathway to improve immunity.
Abstract PD-1 is an inhibitory receptor induced in T cells by antigen stimulation and sustained PD-1 expression plays a key role in T cell dysfunction. Blocking PD-1 signaling rescues exhausted T cells and is an effective treatment for chronic infections and cancer. Nonetheless, combining PD-1 pathway blockade to therapeutic vaccination should further improve T cell rescue. PD-1 is induced shortly after T cell priming, but little is known about the role of PD-1 in the initiation of immune responses. In addition, the PD-1 pathway may also modulate humoral responses, since both B cells and Tfh cells express PD-1. Th...
Source: Current Opinion in Immunology - April 9, 2013 Category: Allergy & Immunology Authors: Kamphorst AO, Ahmed R Tags: Curr Opin Immunol Source Type: research

Dendritic cell-based nanovaccines for cancer immunotherapy.
Abstract Cancer immunotherapy critically relies on the efficient presentation of tumor antigens to T-cells to elicit a potent anti-tumor immune response aimed at life-long protection against cancer recurrence. Recent advances in the nanovaccine field have now resulted in formulations that trigger strong anti-tumor responses. Nanovaccines are assemblies that are able to present tumor antigens and appropriate immune-stimulatory signals either directly to T-cells or indirectly via antigen-presenting dendritic cells. This review focuses on important aspects of nanovaccine design for dendritic cells, including the syne...
Source: Current Opinion in Immunology - April 6, 2013 Category: Allergy & Immunology Authors: Paulis LE, Mandal S, Kreutz M, Figdor CG Tags: Curr Opin Immunol Source Type: research

Genetically engineered mouse models of cancer reveal new insights about the antitumor immune response.
Abstract Cancer is a complex disease that can originate in virtually all the tissues of the body, and tumors progress through many different stages during their development. While genetic mutations in the emerging cancer cells drive this disease, it has become increasingly clear that cancer development is strongly influenced by the surrounding microenvironment. Cells of the immune system are critical components of this extrinsic network of cancer regulators, contributing significantly to the microenvironment of most cancers and either promoting or inhibiting the initiation and progression of this disease. Genetica...
Source: Current Opinion in Immunology - April 1, 2013 Category: Allergy & Immunology Authors: Dupage M, Jacks T Tags: Curr Opin Immunol Source Type: research

Developmental programming of natural killer and innate lymphoid cells.
Abstract In recent years we have witnessed a blooming interest in innate lymphoid cell (ILC) biology thanks to the discovery of novel lineages of ILC that are phenotypically and functionally distinct from NK cells. While the importance of these novel ILC subsets as essential functional components of the early immune responses are now clearly established, many questions remain as to how early ILC developmental fates are determined and how specific effector functions associated with individual ILC subsets are achieved. As the founding member of the ILC family, properties of NK cells have defining attributes that cha...
Source: Current Opinion in Immunology - April 1, 2013 Category: Allergy & Immunology Authors: Vosshenrich CA, Di Santo JP Tags: Curr Opin Immunol Source Type: research

T-bet and Gata3 in controlling type 1 and type 2 immunity mediated by innate lymphoid cells.
Abstract Innate lymphoid cells (ILCs) are an emerging group of innate lymphocytes that share functional and transcriptional attributes with the various T helper cell effector fates (e.g. Th1, Th2, Th17). ILCs are substantially represented in the intestinal mucosa but are rare in secondary lymphoid organs. They play important roles in epithelial homeostasis, tissue repair and in immunity to intestinal infections. They are also involved in immune-mediated pathology. Here, we will review the emerging roles of the transcription factors T-bet and Gata3 in the development, lineage specification and function of distinct ...
Source: Current Opinion in Immunology - April 1, 2013 Category: Allergy & Immunology Authors: Hoyler T, Connor CA, Kiss EA, Diefenbach A Tags: Curr Opin Immunol Source Type: research

Tumour immunology.
PMID: 23510648 [PubMed - in process] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - April 1, 2013 Category: Allergy & Immunology Authors: Dranoff G, Fearon D Tags: Curr Opin Immunol Source Type: research

Combining cancer immunotherapy and targeted therapy.
Abstract The ability to pharmacologically modulate key signaling pathways that drive tumor growth and progression, but do not negatively impact the function of lymphocytes, provides avenues for rational combinatorial approaches to improve the antitumor activity of tumor immunotherapies. Novel targeted agents can very specifically block oncogenic events in cancer cells, leading to a pro-apoptotic milieu and a potential increase in sensitivity to recognition and attack by cytotoxic T lymphocytes (CTLs). Furthermore, targeted pathway modulation in lymphocytes may change their function and have activating effects in s...
Source: Current Opinion in Immunology - April 1, 2013 Category: Allergy & Immunology Authors: Ribas A, Wolchok JD Tags: Curr Opin Immunol Source Type: research

The origin and fate of γδT cell subsets.
The origin and fate of γδT cell subsets. Curr Opin Immunol. 2013 Apr;25(2):181-8 Authors: Kisielow J, Kopf M Abstract Recent experiments indicate that in contrast to αβT cells, γδT cell effector functions are largely preprogrammed in the thymus during fetal life. However the thymus also exports juvenile γδT cells that can mature and be polarized in the periphery. How these developmental pathways are regulated and how much they contribute to the γδT cell effector pool is unclear. Here we discuss recent advances in the understanding of γδ...
Source: Current Opinion in Immunology - April 1, 2013 Category: Allergy & Immunology Authors: Kisielow J, Kopf M Tags: Curr Opin Immunol Source Type: research

Lymphocyte development.
PMID: 23562387 [PubMed - in process] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - April 1, 2013 Category: Allergy & Immunology Authors: Kopf M, Spits H Tags: Curr Opin Immunol Source Type: research

Development and function of group 2 innate lymphoid cells.
Abstract The innate lymphoid cell (ILC) family has recently expanded with the discovery of type-2 innate lymphoid cells (ILC2). These cells arise from lymphoid progenitors in the bone marrow and, under the control of the transcriptional regulators RORα and Gata3, they mature to give rise to IL-5, IL-9 and IL-13 producing ILC2. These cells are critical components of the innate immune response to parasitic worm infections and have also been implicated in the pathogenesis of asthma and allergy. Recent advances in our understanding of the molecular regulation of ILC2 development and function now present the oppo...
Source: Current Opinion in Immunology - April 1, 2013 Category: Allergy & Immunology Authors: Walker JA, McKenzie ANj Tags: Curr Opin Immunol Source Type: research

Human cancer regression antigens.
Abstract Cytotoxic T-cells can recognize antigens that are presented on the surface of human tumor cells and thereby mediate cancer regression. Importantly, those immune interventions that have thus far proven most successful in the clinic-i.e. checkpoint blockade and tumor-infiltrating lymphocyte (TIL) therapy-enhance T-cell activity without a deliberate focus on specific antigens. Thus, one major question remains unsolved: what is the nature of the antigens that need to be recognized on human cancer to result in tumor control? Here we discuss the repertoire of human tumor antigens by three main parameters. First...
Source: Current Opinion in Immunology - April 1, 2013 Category: Allergy & Immunology Authors: Kvistborg P, van Buuren MM, Schumacher TN Tags: Curr Opin Immunol Source Type: research

Noncanonical roles of the immune system in eliciting oncogene addiction.
Abstract Cancer is highly complex. The magnitude of this complexity makes it highly surprising that even the brief suppression of an oncogene can sometimes result in rapid and sustained tumor regression, illustrating that cancers can be 'oncogene addicted' [1-10]. The essential implication is that oncogenes may not only fuel the initiation of tumorigenesis, but in some cases must be excessively activated to maintain a neoplastic state [11]. Oncogene suppression acutely restores normal physiological programs that effectively overrides secondary genetic events and a cancer collapses [12,13]. Oncogene addiction is th...
Source: Current Opinion in Immunology - April 1, 2013 Category: Allergy & Immunology Authors: Casey SC, Bellovin DI, Felsher DW Tags: Curr Opin Immunol Source Type: research

Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment.
Abstract For tumor antigen-specific T cells to effectively control the growth of cancer cells in vivo, they must gain access to, and function within, the tumor microenvironment. While tumor antigen-based vaccines and T cell adoptive transfer strategies can result in clinical benefit in a subset of patients, most of the patients do not respond clinically. Even for tumor-infiltrating lymphocyte (TIL)-based adoptive transfer for patients with metastatic melanoma, which can provide tumor shrinkage in around 50% of treated individuals, many patients are not eligible, in part because there are not sufficient TIL present...
Source: Current Opinion in Immunology - April 1, 2013 Category: Allergy & Immunology Authors: Gajewski TF, Woo SR, Zha Y, Spaapen R, Zheng Y, Corrales L, Spranger S Tags: Curr Opin Immunol Source Type: research

From the immune contexture to the Immunoscore: the role of prognostic and predictive immune markers in cancer.
Abstract The inherent complexity of multifactorial diseases such as cancer renders the process of patient prognosis and prediction of response to therapy extremely difficult. Many markers, signatures, and methods have been described to evaluate the prognosis of cancer patients, yet very few translate into the clinic. Systems biology approaches have facilitated analysis of the complex interaction between tumors and the host-immune response, and allowed the definition of the immune contexture. Here we review the potential of the immune contexture, quantified by the Immunoscore, to provide a statistically strong para...
Source: Current Opinion in Immunology - April 1, 2013 Category: Allergy & Immunology Authors: Angell H, Galon J Tags: Curr Opin Immunol Source Type: research

Cancer immunotherapy.
PMID: 23587868 [PubMed - in process] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - April 1, 2013 Category: Allergy & Immunology Authors: Gajewski TF, Schumacher T Tags: Curr Opin Immunol Source Type: research

The repertoire of human tumor-associated epitopes - identification and selection of antigens and their application in clinical trials.
This article summarizes recent developments in tissue analysis on genome, transcriptome and HLA-ligandome levels and of antigen application in recent clinical vaccination trials. PMID: 23619309 [PubMed - in process] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - April 1, 2013 Category: Allergy & Immunology Authors: Haen SP, Rammensee HG Tags: Curr Opin Immunol Source Type: research

Vaccine against autoimmune disease: antigen-specific immunotherapy.
Abstract Recent interest in testing whether the success of antigen-specific immunotherapy (ASIT) for autoimmune diseases in mice can be translated to humans has highlighted the need for better tools to study and understand human autoimmunity. Clinical development of ASIT for allergy has been instructive, but limited understanding of CD4 T cell epitope/determinant hierarchies hampers the rational design and monitoring of ASIT. Definitive identification of pathogenic T cell epitopes as is now known in celiac disease and recent initiatives to optimize immune monitoring will facilitate rational design, monitoring and ...
Source: Current Opinion in Immunology - March 8, 2013 Category: Allergy & Immunology Authors: Anderson RP, Jabri B Tags: Curr Opin Immunol Source Type: research

Innate and adaptive effects of inflammasomes on T cell responses.
Abstract Inflammasomes are protein complexes that form in response to pathogen-derived or host-derived stress signals. Their activation leads to the production of inflammatory cytokines and promotes a pyrogenic cell death process. The massive release of inflammatory mediators that follows inflammasome activation is a key event in alarming innate immune cells. Growing evidence also highlights the role of inflammasome-dependent cytokines in shaping the adaptive immune response, as exemplified by the capacity of IL-1β to support Th17 responses, or by the finding that IL-18 evokes antigen-independent IFN-γ ...
Source: Current Opinion in Immunology - March 7, 2013 Category: Allergy & Immunology Authors: Dostert C, Ludigs K, Guarda G Tags: Curr Opin Immunol Source Type: research

Vaccine against autoimmune disease: can helminths or their products provide a therapy?
Abstract There is an increasing interest in exploiting the immunomodulatory effects of helminths and their products in treatment of diseases such as allergy, autoimmunity and inflammatory bowel disease. Detailed examination of the ways in which helminth derived products interact with the host immune system and with host physiology has revealed that these may be multifaceted and have almost certainly arisen following co-evolution of helminths and their hosts. Clinical trials have been initiated with encouraging results in the treatment of inflammatory bowel disease and also Multiple Sclerosis. Identification of key...
Source: Current Opinion in Immunology - March 2, 2013 Category: Allergy & Immunology Authors: Zaccone P, Cooke A Tags: Curr Opin Immunol Source Type: research

Damage control: Rorγt+ innate lymphoid cells in tissue regeneration.
Damage control: Rorγt+ innate lymphoid cells in tissue regeneration. Curr Opin Immunol. 2013 Feb 19; Authors: Romera-Hernandez M, Aparicio-Domingo P, Cupedo T Abstract Innate lymphoid cells (ILC) function at the crossroads of innate and adaptive immunity. ILC expressing Rorγt are involved in lymphoid organ formation during embryonic development and mucosal homeostasis and immunity after birth in both mice and man. Mucosal ILC can express natural cytotoxicity receptors NKp44 and NKp46 and produce IL-22, a cytokine pivotal in the control of epithelial innate defenses. The requirements for mouse R...
Source: Current Opinion in Immunology - February 19, 2013 Category: Allergy & Immunology Authors: Romera-Hernandez M, Aparicio-Domingo P, Cupedo T Tags: Curr Opin Immunol Source Type: research

MAIT cells, surveyors of a new class of antigen: development and functions.
Abstract Mucosal associated invariant T (MAIT) cells are evolutionarily conserved T cells that are restricted by the non-classical MHC-1b molecule, MR1. MAIT cells are selected on hematopoietic cells, and exit the thymus with a naïve phenotype before expanding in the periphery and attaining a memory phenotype. MAIT cells represent an abundant oligoclonal population in human blood and liver. MAIT cells react against a newly identified class of antigens: vitamin B metabolites, which are found in most bacteria and yeasts. MAIT cells secrete IFN-γ and IL-17 and their frequencies are modified in several dise...
Source: Current Opinion in Immunology - February 16, 2013 Category: Allergy & Immunology Authors: Le Bourhis L, Mburu YK, Lantz O Tags: Curr Opin Immunol Source Type: research

Inflammatory networks and immune surveillance of pancreatic carcinoma.
Abstract Cancer-associated inflammation plays an important role in restraining anti-tumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA) for which a massive infiltration of immunosuppressive leukocytes into the tumor stroma is an early and consistent event in oncogenesis. Intratumoral effector T cells are rare. This pathophysiology is in contrast to many other solid tumors for which infiltration of effector T cells is often prominent, associated with improved clinical outcomes, and mechanistically contributes to tumor immunoediting that ultimately can mediate immune escape. In PDA, increasing evi...
Source: Current Opinion in Immunology - February 16, 2013 Category: Allergy & Immunology Authors: Vonderheide RH, Bayne LJ Tags: Curr Opin Immunol Source Type: research

The TNFRs OX40, 4-1BB, and CD40 as targets for cancer immunotherapy.
Abstract T cell-mediated rejection of tumors requires signals from the T cell receptor and co-stimulatory molecules to license effector functions of tumor-antigen specific T cells. There is also an array of immune suppressive mechanisms within the tumor microenvironment that can suppress anti-tumor immunity. The use of monoclonal antibodies to overcome this suppression and/or enhance tumor-antigen specific T cell responses has shown promise in clinical trials. In particular, targeting co-stimulatory members of the tumor necrosis factor receptor (TNFR) family with agonist Abs enhances T cell function, which has led...
Source: Current Opinion in Immunology - February 13, 2013 Category: Allergy & Immunology Authors: Moran AE, Kovacsovics-Bankowski M, Weinberg AD Tags: Curr Opin Immunol Source Type: research