Advances In Immunology[JOURNAL]
Sun
200 papers
Humanized Immunoglobulin Mice: Models for HIV Vaccine Testing and Studying the Broadly Neutralizing Antibody Problem.
Verkoczy L
Adv Immunol · 2017 · PMID 28413022 · Full text
A vaccine that can effectively prevent HIV-1 transmission remains paramount to ending the HIV pandemic, but to do so, will likely need to induce broadly neutralizing antibody (bnAb) responses. A major technical hurdle to...
A vaccine that can effectively prevent HIV-1 transmission remains paramount to ending the HIV pandemic, but to do so, will likely need to induce broadly neutralizing antibody (bnAb) responses. A major technical hurdle toward achieving this goal has been a shortage of animal models with the ability to systematically pinpoint roadblocks to bnAb induction and to rank vaccine strategies based on their ability to stimulate bnAb development. Over the past 6 years, immunoglobulin (Ig) knock-in (KI) technology has been leveraged to express bnAbs in mice, an approach that has enabled elucidation of various B-cell tolerance mechanisms limiting bnAb production and evaluation of strategies to circumvent such processes. From these studies, in conjunction with the wealth of information recently obtained regarding the evolutionary pathways and paratopes/epitopes of multiple bnAbs, it has become clear that the very features of bnAbs desired for their function will be problematic to elicit by traditional vaccine paradigms, necessitating more iterative testing of new vaccine concepts. To meet this need, novel bnAb KI models have now been engineered to express either inferred prerearranged V(D)J exons (or unrearranged germline V, D, or J segments that can be assembled into functional rearranged V(D)J exons) encoding predecessors of mature bnAbs. One encouraging approach that has materialized from studies using such newer models is sequential administration of immunogens designed to bind progressively more mature bnAb predecessors. In this review, insights into the regulation and induction of bnAbs based on the use of KI models will be discussed, as will new Ig KI approaches for higher-throughput production and/or altering expression of bnAbs in vivo, so as to further enable vaccine-guided bnAb induction studies.
Regulation of Innate and Adaptive Immunity by TGFβ.
Kelly A, Houston SA, Sherwood E … +2 more , Casulli J, Travis MA
Adv Immunol · 2017 · PMID 28413021 · Publisher ↗
Immune regulation by cytokines is crucial in maintaining immune homeostasis, promoting responses to infection, resolving inflammation, and promoting immunological memory. Additionally, cytokine responses drive pathology...
Immune regulation by cytokines is crucial in maintaining immune homeostasis, promoting responses to infection, resolving inflammation, and promoting immunological memory. Additionally, cytokine responses drive pathology in immune-mediated disease. A crucial cytokine in the regulation of all aspects of an immune response is transforming growth factor beta (TGFβ). Although best known as a crucial regulator of T cell responses, TGFβ plays a vital role in regulating responses mediated by virtually every innate and adaptive immune cell, including dendritic cells, B cells, NK cells, innate lymphoid cells, and granulocytes. Here, we review our current knowledge of how TGFβ regulates the immune system, highlighting the multifunctional nature of TGFβ and how its function can change depending on location and context of action.
γδ T Cells and B Cells.
Born WK, Huang Y, Reinhardt RL … +3 more , Huang H, Sun D, O'Brien RL
Adv Immunol · 2017 · PMID 28413020 · Publisher ↗
γδ T cells constitute the third arm of a tripartite adaptive immune system in jawed vertebrates, besides αβ T cells and B cells. Like the other two lymphocyte-types, they express diverse antigen receptors, capable of spe...
γδ T cells constitute the third arm of a tripartite adaptive immune system in jawed vertebrates, besides αβ T cells and B cells. Like the other two lymphocyte-types, they express diverse antigen receptors, capable of specific ligand recognition. Functionally, γδ T cells represent a system of differentiated subsets, sometimes engaged in cross-regulation, which ultimately determines their effect on other components of the immune system, including B cells and antibodies. γδ T cells are capable of providing help to B cells in antibody production. More recently it became clear that γδ T cells influence B cell differentiation during the peripheral stages of B cell development, control levels of circulating immunoglobulin (all subclasses), and affect production of autoantibodies. Because of this relationship between γδ T cells and B cells, the extensive variation of γδ T cells among human individuals might be expected to modulate their humoral responsiveness.
Emerging Major Histocompatibility Complex Class I-Related Functions of NLRC5.
Chelbi ST, Dang AT, Guarda G
Adv Immunol · 2017 · PMID 28215281 · Publisher ↗
Recent evidence demonstrates a key role for the nucleotide-binding oligomerization domain-like receptor (NLR) family member NLRC5 (NLR family, CARD domain containing protein 5) in the transcriptional regulation of major...
Recent evidence demonstrates a key role for the nucleotide-binding oligomerization domain-like receptor (NLR) family member NLRC5 (NLR family, CARD domain containing protein 5) in the transcriptional regulation of major histocompatibility complex (MHC) class I and related genes. Detailed information on NLRC5 target genes in various cell types and conditions is emerging. Thanks to its analogy to CIITA (class II major MHC transactivator), a NLR family member known for over 20 years to be the master regulator of MHC class II gene transcription, also the molecular mechanisms underlying NLRC5 function are being rapidly unraveled. MHC class I molecules are crucial in regulating innate and adaptive cytotoxic responses. Whereas CD8 T cells detect antigens presented on MHC class I molecules by infected or transformed cells, natural killer (NK) lymphocytes eliminate target cells with downregulated MHC class I expression. Data uncovering the relevance of NLRC5 in homeostasis and activity of these two lymphocyte subsets have been recently reported. Given the importance of CD8 T and NK cells in controlling infection and cancer, it is not surprising that NLRC5 is also starting to emerge as a central player in these diseases. This chapter summarizes and discusses novel insights into the molecular mechanisms underlying NLRC5 activity and its relevance to pathological conditions. A thorough understanding of both aspects is essential to evaluate the clinical significance and therapeutic potential of NLRC5.
Molecular Mechanisms of Somatic Hypermutation and Class Switch Recombination.
Methot SP, Di Noia JM
Adv Immunol · 2017 · PMID 28215280 · Publisher ↗
In order to promote an efficient humoral immune response, germinal center B cells modify both the antigen recognition and effector domains by programmed genetic alterations of their antibody genes. To do so, B cells use...
In order to promote an efficient humoral immune response, germinal center B cells modify both the antigen recognition and effector domains by programmed genetic alterations of their antibody genes. To do so, B cells use the enzyme activation-induced deaminase (AID), which transforms deoxycytidine into deoxyuridine at the immunoglobulin genes, triggering mutagenic DNA repair. Data accumulated during the past decade have significantly advanced our understanding of how AID activity is regulated and preferentially targeted to the immunoglobulin genes. There is also a better understanding of the ways by which AID-catalyzed uracil is recognized and the ensuing downstream processing underpinning the mechanisms of somatic hypermutation and class switch recombination. Here, we critically review these advances in the context of their relevance for the humoral immune response. A detailed understanding of these molecular mechanisms is paramount to uncover the basis of B cell intrinsic immunodeficiency, as well as to suggest tools and strategies that might allow boosting antibody gene diversification in the context of immunizations or infections that require the elicitation of rare or highly mutated antibody variants.
About Training and Memory: NK-Cell Adaptation to Viral Infections.
Hammer Q, Romagnani C
Adv Immunol · 2017 · PMID 28215279 · Publisher ↗
Viral infections continuously challenge and shape our immune system. Due to their fine antigen recognition ability, adaptive lymphocytes protect against pathogen reencounter by generating specific immunological memory. I...
Viral infections continuously challenge and shape our immune system. Due to their fine antigen recognition ability, adaptive lymphocytes protect against pathogen reencounter by generating specific immunological memory. Innate cells such as macrophages also adapt to pathogen challenge and mount resistance to reinfection, a phenomenon termed trained immunity. As part of the innate immunity, natural killer (NK) cells can display rapid effector functions and play a crucial role in the control of viral infections, especially by the β-herpesvirus cytomegalovirus (CMV). CMV activates the NK-cell pool by inducing proinflammatory signals, which prime NK cells, paralleling macrophage training. In addition, CMV dramatically shapes the NK-cell repertoire due to its ability to trigger specific NK cell-activating receptors, and enables the expansion and persistence of a specific NK-cell subset displaying adaptive and memory features. In this chapter, we will discuss how different signals during CMV infection contribute to NK-cell training and acquisition of classical memory properties and how these events can impact on reinfection and cross-resistance.
Nucleic Acid Immunity.
Hartmann G
Adv Immunol · 2017 · PMID 28215278 · Full text
Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its...
Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its function and replication. Tremendous progress has been made in the understanding of these mechanisms which keep foreign or unwanted nucleic acids from viruses or phages in check. Mechanisms reach from restriction-modification systems and CRISPR/Cas in bacteria and archaea to RNA interference and immune sensing of nucleic acids, altogether integral parts of a system which is now appreciated as nucleic acid immunity. With inherited receptors and acquired sequence information, nucleic acid immunity comprises innate and adaptive components. Effector functions include diverse nuclease systems, intrinsic activities to directly restrict the function of foreign nucleic acids (e.g., PKR, ADAR1, IFIT1), and extrinsic pathways to alert the immune system and to elicit cytotoxic immune responses. These effects act in concert to restrict viral replication and to eliminate virus-infected cells. The principles of nucleic acid immunity are highly relevant for human disease. Besides its essential contribution to antiviral defense and restriction of endogenous retroelements, dysregulation of nucleic acid immunity can also lead to erroneous detection and response to self nucleic acids then causing sterile inflammation and autoimmunity. Even mechanisms of nucleic acid immunity which are not established in vertebrates are relevant for human disease when they are present in pathogens such as bacteria, parasites, or helminths or in pathogen-transmitting organisms such as insects. This review aims to provide an overview of the diverse mechanisms of nucleic acid immunity which mostly have been looked at separately in the past and to integrate them under the framework nucleic acid immunity as a basic principle of life, the understanding of which has great potential to advance medicine.
Macrophages and Mitochondria: A Critical Interplay Between Metabolism, Signaling, and the Functional Activity.
Tur J, Vico T, Lloberas J … +2 more , Zorzano A, Celada A
Adv Immunol · 2017 · PMID 28215277 · Publisher ↗
Macrophages are phagocytic cells that participate in a broad range of cellular functions and they are key regulators of innate immune responses and inflammation. Mitochondria are highly dynamic endosymbiotic organelles t...
Macrophages are phagocytic cells that participate in a broad range of cellular functions and they are key regulators of innate immune responses and inflammation. Mitochondria are highly dynamic endosymbiotic organelles that play key roles in cellular metabolism and apoptosis. Mounting evidence suggests that mitochondria are involved in the interplay between metabolism and innate immune responses. The ability of these organelles to alter the metabolic profile of a cell, thereby allowing an appropriate response to each situation, is crucial for the correct establishment of immune responses. Furthermore, mitochondria act as scaffolds for many proteins involved in immune signaling pathways and as such they are able to modulate the function of these proteins. Finally, mitochondria release molecules, such as reactive oxygen species, which directly regulate the immune response. In summary, mitochondria can be considered as core components in the regulation of innate immune signaling. Here we discuss the intricate relationship between mitochondria, metabolism, intracellular signaling, and innate immune responses in macrophages.
The Roles of the Secreted Phospholipase A Gene Family in Immunology.
Murakami M, Yamamoto K, Miki Y … +3 more , Murase R, Sato H, Taketomi Y
Adv Immunol · 2016 · PMID 27769509 · Full text
Within the phospholipase A (PLA) family that hydrolyzes phospholipids to yield fatty acids and lysophospholipids, secreted PLA (sPLA) enzymes comprise the largest group containing 11 isoforms in mammals. Individual sPLAs...
Within the phospholipase A (PLA) family that hydrolyzes phospholipids to yield fatty acids and lysophospholipids, secreted PLA (sPLA) enzymes comprise the largest group containing 11 isoforms in mammals. Individual sPLAs exhibit unique tissue or cellular distributions and enzymatic properties, suggesting their distinct biological roles. Although PLA enzymes, particularly cytosolic PLA (cPLAα), have long been implicated in inflammation by driving arachidonic acid metabolism, the precise biological roles of sPLAs have remained a mystery over the last few decades. Recent studies employing mice gene-manipulated for individual sPLAs, in combination with mass spectrometric lipidomics to identify their target substrates and products in vivo, have revealed their roles in diverse biological events, including immunity and associated disorders, through lipid mediator-dependent or -independent processes in given microenvironments. In this review, we summarize our current knowledge of the roles of sPLAs in various immune responses and associated diseases.
B-Lymphopoiesis in Fetal Liver, Guided by Chemokines.
Kajikhina K, Tsuneto M, Melchers F
Adv Immunol · 2016 · PMID 27769508 · Publisher ↗
Early in embryonic development of mice, from day 12.5 after conception, myeloid-lymphoid bipotent progenitors, expressing receptors both for IL7 and CSF-1, migrate from embryonic blood into developing fetal liver. These...
Early in embryonic development of mice, from day 12.5 after conception, myeloid-lymphoid bipotent progenitors, expressing receptors both for IL7 and CSF-1, migrate from embryonic blood into developing fetal liver. These progenitors also express multiple chemokine receptors, i.e., CCR7, CXCR3, CXCR4, and CXCR5, all on one cell. Their migration through LYVE-1+ vascular endothelium is guided by CCR7, recognizing the chemokine CCL19, and by CXCR3, recognizing CXCL10/11, chemokines which are both produced by the endothelium. Once inside fetal liver, the progenitors are attracted by the chemokine CXCL12 to ALCAM+ liver mesenchyme, which produces not only this chemokine, but also the myeloid differentiation-inducing cytokine CSF-1 and the lymphoid differentiation-inducing cytokine IL7. In this mesenchymal environment B-lymphocyte lineage progenitors are then induced by IL7 to enter differentiation and Ig gene rearrangements. Within 3-4 days surface IgM+ immature B-cells develop, which are destined to enter the B1-cell compartments in the peripheral lymphoid organs.
Endogenous Retroelements and the Host Innate Immune Sensors.
Mu X, Ahmad S, Hur S
Adv Immunol · 2016 · PMID 27769507 · Full text
The ability to distinguish between self and nonself is the fundamental basis of the immune system in all organisms. The conceptual distinction between self and nonself, however, breaks down when it comes to endogenous re...
The ability to distinguish between self and nonself is the fundamental basis of the immune system in all organisms. The conceptual distinction between self and nonself, however, breaks down when it comes to endogenous retroviruses and other retroelements. While some retroelements retain the virus-like features including the capacity to replicate and reinvade the host genome, most have become inactive through mutations or host epigenetic silencing. And yet, accumulating evidence suggests that endogenous retroelements, both active and inactive, play important roles not only in pathogenesis of immune disorders, but also in proper functioning of the immune system. This review discusses the recent development in our understanding of the interaction between retroelements and the host innate immune system. In particular, it focuses on the impact of retroelement transcripts on the viral RNA sensors such as Toll-like receptors, RIG-I-like receptors, protein kinase R, and the inflammasomes.
Pleiotropic Roles of Type 1 Interferons in Antiviral Immune Responses.
Teijaro JR
Adv Immunol · 2016 · PMID 27769506 · Full text
Since Isaac's and Lindenmann's seminal experiments over 50 years ago demonstrating a soluble factor generated from heat killed virus-stimulated chicken embryos could inhibit live influenza virus replication, the term int...
Since Isaac's and Lindenmann's seminal experiments over 50 years ago demonstrating a soluble factor generated from heat killed virus-stimulated chicken embryos could inhibit live influenza virus replication, the term interferon has been synonymous with inhibition of virus replication. While the antiviral properties of type 1 interferon (IFN-I) are undeniable, recent studies have reported expanding and somewhat unexpected roles of IFN-I signaling during both acute and persistent viral infections. IFN-I signaling can promote morbidity and mortality through induction of aberrant inflammatory responses and recruitment of inflammatory innate immune cell populations during acute respiratory viral infections. During persistent viral infection, IFN-I signaling promotes containment of early viral replication/dissemination, however, also initiates and maintains immune suppression, lymphoid tissue disorganization, and CD4 T cell dysfunction through modulation of multiple immune cell populations. Finally, new data are emerging illuminating how specific IFN-I species regulate immune pathology and suppression during acute and persistent viral infections, respectively. Systematic characterization of the cellular populations that produce IFN-I, how the timing of IFN-I induction and intricacies of subtype specific IFN-I signaling promote pathology or immune suppression during acute and persistent viral infections should inform the development of treatments and modalities to control viral associated pathologies.
Context- and Tissue-Specific Regulation of Immunity and Tolerance by Regulatory T Cells.
Ulges A, Schmitt E, Becker C … +1 more , Bopp T
Adv Immunol · 2016 · PMID 27769505 · Publisher ↗
The immune system has evolved to defend the organism against an almost infinite number of pathogens in a locally confined and antigen-specific manner while at the same time preserving tolerance to harmless antigens and s...
The immune system has evolved to defend the organism against an almost infinite number of pathogens in a locally confined and antigen-specific manner while at the same time preserving tolerance to harmless antigens and self. Regulatory T (Treg) cells essentially contribute to an immunoregulatory network preventing excessive immune responses and immunopathology. There is emerging evidence that Treg cells not only operate in secondary lymphoid tissue but also regulate immune responses directly at the site of inflammation. Hence, the classification of Treg cells might need to be further extended by Treg cell subsets that are functionally and phenotypically polarized by their residency. In this review, we discuss recent findings on these tissue-resident Treg cell subsets and how these cells may operate in a tissue- and context-dependent manner.
Advances in PET Detection of the Antitumor T Cell Response.
McCracken MN, Tavaré R, Witte ON … +1 more , Wu AM
Adv Immunol · 2016 · PMID 27235684 · Full text
Positron emission tomography (PET) is a powerful noninvasive imaging technique able to measure distinct biological processes in vivo by administration of a radiolabeled probe. Whole-body measurements track the probe accu...
Positron emission tomography (PET) is a powerful noninvasive imaging technique able to measure distinct biological processes in vivo by administration of a radiolabeled probe. Whole-body measurements track the probe accumulation providing a means to measure biological changes such as metabolism, cell location, or tumor burden. PET can also be applied to both preclinical and clinical studies providing three-dimensional information. For immunotherapies (in particular understanding T cell responses), PET can be utilized for spatial and longitudinal tracking of T lymphocytes. Although PET has been utilized clinically for over 30 years, the recent development of additional PET radiotracers have dramatically expanded the use of PET to detect endogenous or adoptively transferred T cells in vivo. Novel probes have identified changes in T cell quantity, location, and function. This has enabled investigators to track T cells outside of the circulation and in hematopoietic organs such as spleen, lymph nodes, and bone marrow, or within tumors. In this review, we cover advances in PET detection of the antitumor T cell response and areas of focus for future studies.
Germinal Center B-Cell-Associated Nuclear Protein (GANP) Involved in RNA Metabolism for B Cell Maturation.
Sakaguchi N, Maeda K
Adv Immunol · 2016 · PMID 27235683 · Publisher ↗
Germinal center B-cell-associated nuclear protein (GANP) is upregulated in germinal center B cells against T-cell-dependent antigens in mice and humans. In mice, GANP depletion in B cells impairs antibody affinity matura...
Germinal center B-cell-associated nuclear protein (GANP) is upregulated in germinal center B cells against T-cell-dependent antigens in mice and humans. In mice, GANP depletion in B cells impairs antibody affinity maturation. Conversely, its transgenic overexpression augments the generation of high-affinity antigen-specific B cells. GANP associates with AID in the cytoplasm, shepherds AID into the nucleus, and augments its access to the rearranged immunoglobulin (Ig) variable (V) region of the genome in B cells, thereby precipitating the somatic hypermutation of V region genes. GANP is also upregulated in human CD4(+) T cells and is associated with APOBEC3G (A3G). GANP interacts with A3G and escorts it to the virion cores to potentiate its antiretroviral activity by inactivating HIV-1 genomic cDNA. Thus, GANP is characterized as a cofactor associated with AID/APOBEC cytidine deaminase family molecules in generating diversity of the IgV region of the genome and genetic alterations of exogenously introduced viral targets. GANP, encoded by human chromosome 21, as well as its mouse equivalent on chromosome 10, contains a region homologous to Saccharomyces Sac3 that was characterized as a component of the transcription/export 2 (TREX-2) complex and was predicted to be involved in RNA export and metabolism in mammalian cells. The metabolism of RNA during its maturation, from the transcription site at the chromosome within the nucleus to the cytoplasmic translation apparatus, needs to be elaborated with regard to acquired and innate immunity. In this review, we summarize the current knowledge on GANP as a component of TREX-2 in mammalian cells.
Deep Profiling Human T Cell Heterogeneity by Mass Cytometry.
Cheng Y, Newell EW
Adv Immunol · 2016 · PMID 27235682 · Publisher ↗
Advances of mass cytometry and high-dimensional single-cell data analysis have brought cellular immunological research into a new generation. By coupling these two powerful technology platforms, immunologists now have mo...
Advances of mass cytometry and high-dimensional single-cell data analysis have brought cellular immunological research into a new generation. By coupling these two powerful technology platforms, immunologists now have more tools to resolve the tremendous diversity of immune cell subsets, and their heterogeneous functionality. Since the first introduction of mass cytometry, many reports have been published using this novel technology to study a range of cell types. At the outset, studies of human hematopoietic stem cell and peripheral CD8(+) T cells using mass cytometry have shad the light of future experimental approach in interrogating immune cell phenotypic and functional diversity. Here, we briefly revisit the past and present understanding of T cell heterogeneity, and the technologies that facilitate this knowledge. In addition, we review the current progress of mass cytometry and high-dimensional cytometric analysis, including the methodology, panel design, experimental procedure, and choice of computational algorithms with a special focus on their utility in exploration of human T cell immunology.
Factors That Regulate the Generation of Antibody-Secreting Plasma Cells.
Yu YH, Lin KI
Adv Immunol · 2016 · PMID 27235681 · Publisher ↗
The generation of antigen-specific neutralizing antibodies and memory B cells is one of the most important immune protections of the host and is the basis for successful vaccination strategies. The protective antibodies,...
The generation of antigen-specific neutralizing antibodies and memory B cells is one of the most important immune protections of the host and is the basis for successful vaccination strategies. The protective antibodies, secreted by preexisting long-lived plasma cells and reactivated antigen-experienced memory B cells, constitute the main humoral immune defense. Distinct from the primary antibody response, the humoral memory response is generated much faster and with greater magnitude, and it produces antibodies with higher affinity and variable isotypes. Humoral immunity is critically dependent on the germinal center where high-affinity memory B cells and plasma cells are generated. In this chapter, we focus on recent advances in our understanding of the molecular mechanisms that govern fate decision for memory B cells and plasma cells and the mechanisms that maintain the long-lived plasma-cell pool, with emphasis on how the transcription factor Blimp-1 (B lymphocyte-induced maturation protein-1) helps regulate the above-mentioned immunoregulatory steps to ensure the production and maintenance of antibody-secreting plasma cells as well as how it directs memory cell vs plasma-cell fate. We also discuss the molecular basis of Blimp-1 action and how its expression is regulated.
Malondialdehyde Epitopes as Targets of Immunity and the Implications for Atherosclerosis.
Papac-Milicevic N, Busch CJ, Binder CJ
Adv Immunol · 2016 · PMID 27235680 · Full text
Accumulating evidence suggests that oxidation-specific epitopes (OSEs) constitute a novel class of damage-associated molecular patterns (DAMPs) generated during high oxidative stress but also in the physiological process...
Accumulating evidence suggests that oxidation-specific epitopes (OSEs) constitute a novel class of damage-associated molecular patterns (DAMPs) generated during high oxidative stress but also in the physiological process of apoptosis. To deal with the potentially harmful consequences of such epitopes, the immune system has developed several mechanisms to protect from OSEs and to orchestrate their clearance, including IgM natural antibodies and both cellular- and membrane-bound receptors. Here, we focus on malondialdehyde (MDA) epitopes as prominent examples of OSEs that trigger both innate and adaptive immune responses. First, we review the mechanisms of MDA generation, the different types of adducts on various biomolecules and provide relevant examples for physiological carriers of MDA such as apoptotic cells, microvesicles, or oxidized low-density lipoproteins. Based on recent insights, we argue that MDA epitopes contribute to the maintenance of homeostatic functions by acting as markers of elevated oxidative stress and tissue damage. We discuss multiple lines of evidence that MDA epitopes are proinflammatory and thus important targets of innate and adaptive immune responses. Finally, we illustrate the relevance of MDA epitopes in human pathologies by describing their capacity to drive inflammatory processes in atherosclerosis and highlighting protective mechanisms of immunity that could be exploited for therapeutic purposes.
Preface.
Schreiber RD
Adv Immunol · 2016 · PMID 26923005 · Publisher ↗
Abstract loading — click title to view on PubMed.
Adoptive T-Cell Therapy for Cancer.
Yang JC, Rosenberg SA
Adv Immunol · 2016 · PMID 26923004 · Full text
Recent developments have demonstrated that immunotherapies are capable of achieving durable antitumor responses in patients with metastatic cancer. One modality that has been able to induce durable complete regressions i...
Recent developments have demonstrated that immunotherapies are capable of achieving durable antitumor responses in patients with metastatic cancer. One modality that has been able to induce durable complete regressions in patients with melanoma has been adoptive cell therapy (ACT). This has slowly been expanded to other cancer types using new approaches such as genetically engineered T-cells and other methods of antigen targeting. It now appears that immune targeting of mutated "neoantigens" plays a major role in successful ACT, as well as in other immunotherapies such as checkpoint inhibitors. This realization presents not only new challenges to ACT but also new opportunities in that all tumors now may have potential antigens to attack that can be revealed by tumor genomic sequencing. There are a variety of exciting approaches to translate these new findings into clinical trials applying ACT to the majority of cancer types.
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