Advances In Immunology[JOURNAL]
Sun
200 papers
System-level integrative omics analysis to identify the virus-host immunometabolic footprint during infection.
Ambikan A, Akusjärvi SS, Sperk M … +1 more , Neogi U
Adv Immunol · 2024 · PMID 39523029 · Publisher ↗
The emergence and re-emergence of infectious diseases present significant global health threats. Understanding their pathogenesis is crucial for developing diagnostics, therapeutics, and preventive strategies. System-lev...
The emergence and re-emergence of infectious diseases present significant global health threats. Understanding their pathogenesis is crucial for developing diagnostics, therapeutics, and preventive strategies. System-level integrative omics analysis offers a comprehensive approach to deciphering virus-host immunometabolic interactions during infections. Multi-omics approaches, integrating genomics, transcriptomics, proteomics, and metabolomics, provide holistic insights into disease mechanisms, host-pathogen interactions, and immune responses. The interplay between the immune system and metabolic processes, termed immunometabolism, has gained attention, particularly in infectious diseases. Immunometabolic studies reveal how metabolic processes regulate immune cell function, shaping immune responses and influencing infection outcomes. Metabolic reprogramming is crucial for immune cell activation, differentiation, and function. Using systems biological algorithms to understand the immunometabolic alterations can provide a holistic view of immune and metabolic pathway interactions, identifying regulatory nodes and predicting responses to perturbations. Understanding these pathways enhances the knowledge of immune regulation and offers avenues for therapeutic interventions. This review highlights the contributions of multi-omics systems biology studies in understanding infectious disease pathogenesis, focusing on RNA viruses. The integrative approach enables personalized medicine strategies, considering individual metabolic and immune variations. Leveraging these interdisciplinary approaches promises advancements in combating RNA virus infections and improving health outcomes, highlighting the transformative impact of multi-omics technologies in infectious disease research.
The multifaceted roles of TCF1 in innate and adaptive lymphocytes.
McCullen M, Oltz E
Adv Immunol · 2024 · PMID 39523028 · Full text
The immune system requires a complex network of specialized cell types to defend against a range of threats. The specific roles and destinies of these cell types are enforced by a constellation of gene regulatory program...
The immune system requires a complex network of specialized cell types to defend against a range of threats. The specific roles and destinies of these cell types are enforced by a constellation of gene regulatory programs, which are orchestrated through lineage-specifying transcription factors. T Cell Factor 1 (TCF1) is a central transcription factor in many of these programs, guiding the development and functionality of both adaptive and innate lymphoid cells. This review highlights recent insights into the function of TCF1 in a variety of lymphoid cell subsets and its potential for translational applications in immune disorders and cancer.
Unravelling the contribution of lymph node fibroblasts to vaccine responses.
Cinti I, Vezyrgianni K, Denton AE
Adv Immunol · 2024 · PMID 39523027 · Publisher ↗
Vaccination is one of the most effective medical interventions, saving millions of lives and reducing the morbidity of infections across the lifespan, from infancy to older age. The generation of plasma cells and memory...
Vaccination is one of the most effective medical interventions, saving millions of lives and reducing the morbidity of infections across the lifespan, from infancy to older age. The generation of plasma cells and memory B cells that produce high affinity class switched antibodies is central to this protection, and these cells are the ultimate output of the germinal centre response. Optimal germinal centre responses require different immune cells to interact with one another in the right place and at the right time and this delicate cellular ballet is coordinated by a network of interconnected stromal cells. In this review we will discuss the various types of lymphoid stromal cells and how they coordinate immune cell homeostasis, the induction and maintenance of the germinal centre response, and how this is disorganised in older bodies.
Anatomy of a superenhancer.
Kim S, Liu TT, Ou F … +2 more , Murphy TL, Murphy KM
Adv Immunol · 2024 · PMID 39271259 · Publisher ↗
Interferon regulatory factor-8 (IRF8) is the lineage determining transcription factor for the type one classical dendritic cell (cDC1) subset, a terminal selector for plasmacytoid dendritic cells and important for the fu...
Interferon regulatory factor-8 (IRF8) is the lineage determining transcription factor for the type one classical dendritic cell (cDC1) subset, a terminal selector for plasmacytoid dendritic cells and important for the function of monocytes. Studies of Irf8 gene regulation have identified several enhancers controlling its activity during development of progenitors in the bone marrow that precisely regulate expression at distinct developmental stages. Each enhancer responds to distinct transcription factors that are expressed at each stage. IRF8 is first expressed in early progenitors that form the monocyte dendritic cell progenitor (MDP) in response to induction of the transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) acting at the Irf8 +56 kb enhancer. IRF8 levels increase further as the MDP transits into the common dendritic cell progenitor (CDP) in response to E protein activity at the Irf8 +41 kb enhancer. Upon Nfil3-induction in CDPs leading to specification of the cDC1 progenitor, abrupt induction of BATF3 forms the JUN/BATF3/IRF8 heterotrimer that activates the Irf8 +32 kb enhancer that sustains Irf8 autoactivation throughout the cDC1 lifetime. Deletions of each of these enhancers has revealed their stage dependent activation. Surprisingly, studies of compound heterozygotes for each combination of enhancer deletions revealed that activation of each subsequent enhancer requires the successful activation of the previous enhancer in strictly cis-dependent mechanism. Successful progression of enhancer activation is finely tuned to alter the functional accessibility of subsequent enhancers to factors active in the next stage of development. The molecular basis for these phenomenon is still obscure but could have implications for genomic regulation in a broader developmental context.
IL-17 family cytokines in inflammatory or autoimmune skin diseases.
Kong B, Lai Y
Adv Immunol · 2024 · PMID 39271258 · Publisher ↗
As potent pro-inflammatory mediators, IL-17 family cytokines play crucial roles in the pathogenesis of various inflammatory and autoimmune skin disorders. Although substantial progress has been achieved in understanding...
As potent pro-inflammatory mediators, IL-17 family cytokines play crucial roles in the pathogenesis of various inflammatory and autoimmune skin disorders. Although substantial progress has been achieved in understanding the pivotal role of IL-17A signaling in psoriasis, leading to the development of highly effective biologics, the functions of other IL-17 family members in inflammatory or autoimmune skin diseases remain less explored. In this review, we provide a comprehensive overview of IL-17 family cytokines and their receptors, with a particular focus on the recent advancements in identifying cellular sources, receptors and signaling pathways regulated by these cytokines. At the end, we discuss how the aberrant functions of IL-17 family cytokines contribute to the pathogenesis of diverse inflammatory or autoimmune skin diseases.
The role of autophagy in RIP1 mediated cell death and intestinal inflammation.
Lee YM, Vucic D
Adv Immunol · 2024 · PMID 39271257 · Publisher ↗
Autophagy, a highly conserved catabolic process that targets various types of cellular cargoes to lysosomal degradation, is one of the most important biological mechanisms critical for cellular homeostasis. Components of...
Autophagy, a highly conserved catabolic process that targets various types of cellular cargoes to lysosomal degradation, is one of the most important biological mechanisms critical for cellular homeostasis. Components of these cellular cargoes can range from individual proteins to invading pathogens, and degrading these materials is important for maintaining organismal health and survival. The process of autophagy is carried out by complex molecular mechanisms, and a growing body of evidence indicates that these mechanisms intersect with those involved in the cell death pathways. In this review, we examine several emerging studies elucidating the role of autophagy in RIP1-mediated cell death signaling, with particular emphasis on impaired autophagy caused by ATG16L1 deficiency. We also discuss how autophagy in RIP1-mediated cell death affects intestinal homeostasis in preclinical models, and the implications of the intersection between RIP1 and autophagy for understanding the intestinal pathologies associated with inflammatory bowel disease (IBD). Finally, we highlight the potential benefits of therapeutic targeting of RIP1 and autophagy proteins, while also proposing areas of research that will likely elucidate new links between autophagy and cell death signaling.
The regulation of the apoptotic pore-An immunological tightrope walk.
Jenner A, Garcia-Saez AJ
Adv Immunol · 2024 · PMID 38866439 · Publisher ↗
Apoptotic pore formation in mitochondria is the pivotal point for cell death during mitochondrial apoptosis. It is regulated by BCL-2 family proteins in response to various cellular stress triggers and mediates mitochond...
Apoptotic pore formation in mitochondria is the pivotal point for cell death during mitochondrial apoptosis. It is regulated by BCL-2 family proteins in response to various cellular stress triggers and mediates mitochondrial outer membrane permeabilization (MOMP). This allows the release of mitochondrial contents into the cytosol, which triggers rapid cell death and clearance through the activation of caspases. However, under conditions of low caspase activity, the mitochondrial contents released into the cytosol through apoptotic pores serve as inflammatory signals and activate various inflammatory responses. In this chapter, we discuss how the formation of the apoptotic pore is regulated by BCL-2 proteins as well as other cellular or mitochondrial proteins and membrane lipids. Moreover, we highlight the importance of sublethal MOMP in the regulation of mitochondrial-activated inflammation and discuss its physiological consequences in the context of pathogen infection and disease and how it can potentially be exploited therapeutically, for example to improve cancer treatment.
Crosstalk between CD8 T cells and mesenchymal stromal cells in intestine homeostasis and immunity.
Chen Y, Sun H, Luo Z … +8 more , Mei Y, Xu Z, Tan J, Xie Y, Li M, Xia J, Yang B, Su B
Adv Immunol · 2024 · PMID 38866438 · Publisher ↗
The intestine represents the most complex cellular network in the whole body. It is constantly faced with multiple types of immunostimulatory agents encompassing from food antigen, gut microbiome, metabolic waste product...
The intestine represents the most complex cellular network in the whole body. It is constantly faced with multiple types of immunostimulatory agents encompassing from food antigen, gut microbiome, metabolic waste products, and dead cell debris. Within the intestine, most T cells are found in three primary compartments: the organized gut-associated lymphoid tissue, the lamina propria, and the epithelium. The well-orchestrated epithelial-immune-microbial interaction is critically important for the precise immune response. The main role of intestinal mesenchymal stromal cells is to support a structural framework within the gut wall. However, recent evidence from stromal cell studies indicates that they also possess significant immunomodulatory functions, such as maintaining intestinal tolerance via the expression of PDL1/2 and MHC-II molecules, and promoting the development of CD103 dendritic cells, and IgA plasma cells, thereby enhancing intestinal homeostasis. In this review, we will summarize the current understanding of CD8 T cells and stromal cells alongside the intestinal tract and discuss the reciprocal interactions between T subsets and mesenchymal stromal cell populations. We will focus on how the tissue residency, migration, and function of CD8 T cells could be potentially regulated by mesenchymal stromal cell populations and explore the molecular mediators, such as TGF-β, IL-33, and MHC-II molecules that might influence these processes. Finally, we discuss the potential pathophysiological impact of such interaction in intestine hemostasis as well as diseases of inflammation, infection, and malignancies.
Germinal center versus extrafollicular responses in systemic autoimmunity: Who turns the blade on self?
He Y, Vinuesa CG
Adv Immunol · 2024 · PMID 38866437 · Full text
Spontaneously formed germinal centers (GCs) have been reported in most mouse models of human autoimmune disease and autoimmune patients, and have long been considered a source of somatically-mutated and thus high affinit...
Spontaneously formed germinal centers (GCs) have been reported in most mouse models of human autoimmune disease and autoimmune patients, and have long been considered a source of somatically-mutated and thus high affinity autoantibodies, but their role in autoimmunity is becoming increasingly controversial, particularly in the context of systemic autoimmune diseases like lupus. On the one hand, there is good evidence that some pathogenic lupus antibodies have acquired somatic mutations that increase affinity for self-antigens. On the other hand, recent studies that have genetically prevented GC formation, suggest that GCs are dispensable for systemic autoimmunity, pointing instead to pathogenic extrafollicular (EF) B-cell responses. Furthermore, several lines of evidence suggest germinal centers may in fact be somewhat protective in the context of autoimmunity. Here we review how some of the conflicting evidence arose, and current views on the role of GCs in autoimmunity, outlining mechanisms by which GC may eliminate self-reactivity. We also discuss recent advances in understanding extrafollicular B cell subsets that participate in autoimmunity.
The molecular mechanism of dsDNA sensing through the cGAS-STING pathway.
Shinde O, Li P
Adv Immunol · 2024 · PMID 38866436 · Publisher ↗
Double stranded DNA (dsDNA) in the cytoplasm triggers the cGAS-STING innate immune pathway to defend against pathogenic infections, tissue damage and malignant cells. Extensive structural and functional studies over the...
Double stranded DNA (dsDNA) in the cytoplasm triggers the cGAS-STING innate immune pathway to defend against pathogenic infections, tissue damage and malignant cells. Extensive structural and functional studies over the last couple of years have enabled the molecular understanding of dsDNA induced activation of the cGAS-STING signaling pathway. This review highlights recent advances in the structural characterization of key molecules in the cGAS-STING signaling axis by focusing on the mechanism of cGAS activation by dsDNA, the regulation of cGAS activity, the mechanism of STING activation by cGAMP, the molecular basis of TBK1 recruitment and activation by STING, the structural basis of IRF3 recruitment by STING, and the mechanism of IRF3 activation upon phosphorylation by TBK1. These comprehensive structural studies provide a detailed picture of the mechanism of the cGAS-STING signaling pathway, establishing a molecular framework for the development of novel therapeutic strategies targeting this pathway.
Post-transcriptional (re)programming of B lymphocyte development: From bench to bedside?
Welsh AM, Muljo SA
Adv Immunol · 2024 · PMID 38763703 · Full text
Hematopoiesis, a process which generates blood and immune cells, changes significantly during mammalian development. Definitive hematopoiesis is marked by the emergence of long-term hematopoietic stem cells (HSCs). Here,...
Hematopoiesis, a process which generates blood and immune cells, changes significantly during mammalian development. Definitive hematopoiesis is marked by the emergence of long-term hematopoietic stem cells (HSCs). Here, we will focus on the post-transcriptional differences between fetal liver (FL) and adult bone marrow (ABM) HSCs. It remains unclear how or why exactly FL HSCs transition to ABM HSCs, but we aim to leverage their differences to revive an old idea: in utero HSC transplantation. Unexpectedly, the expression of certain RNA-binding proteins (RBPs) play an important role in HSC specification, and can be employed to convert or reprogram adult HSCs back to a fetal-like state. Among other features, FL HSCs have a broad differentiation capacity that includes the ability to regenerate both conventional B and T cells, as well as innate-like or unconventional lymphocytes such as B-1a and marginal zone B (MzB) cells. This chapter will focus on RNA binding proteins, namely LIN28B and IGF2BP3, that are expressed during fetal life and how they promote B-1a cell development. Furthermore, this chapter considers a potential clinical application of synthetic co-expression of LIN28B and IGF2BP3 in HSCs.
The Sixth Sense: Self-nucleic acid sensing in the brain.
Dorrity TJ, Shin H, Gertie JA … +1 more , Chung H
Adv Immunol · 2024 · PMID 38763702 · Full text
Our innate immune system uses pattern recognition receptors (PRRs) as a first line of defense to detect microbial ligands and initiate an immune response. Viral nucleic acids are key ligands for the activation of many PR...
Our innate immune system uses pattern recognition receptors (PRRs) as a first line of defense to detect microbial ligands and initiate an immune response. Viral nucleic acids are key ligands for the activation of many PRRs and the induction of downstream inflammatory and antiviral effects. Initially it was thought that endogenous (self) nucleic acids rarely activated these PRRs, however emerging evidence indicates that endogenous nucleic acids are able to activate host PRRs in homeostasis and disease. In fact, many regulatory mechanisms are in place to finely control and regulate sensing of self-nucleic acids by PRRs. Sensing of self-nucleic acids is particularly important in the brain, as perturbations to nucleic acid sensing commonly leads to neuropathology. This review will highlight the role of nucleic acid sensors in the brain, both in disease and homeostasis. We also indicate the source of endogenous stimulatory nucleic acids where known and summarize future directions for the study of this growing field.
Innate immune sensing of macromolecule homeostasis.
Yang K, Jeltema D, Yan N
Adv Immunol · 2024 · PMID 38763701 · Publisher ↗
The innate immune system uses a distinct set of germline-encoded pattern recognition receptors to recognize molecular patterns initially thought to be unique to microbial invaders, named pathogen-associated molecular pat...
The innate immune system uses a distinct set of germline-encoded pattern recognition receptors to recognize molecular patterns initially thought to be unique to microbial invaders, named pathogen-associated molecular patterns. The concept was later further developed to include similar molecular patterns originating from host cells during tissue damage, known as damage-associated molecular patterns. However, recent advances in the mechanism of monogenic inflammatory diseases have highlighted a much more expansive repertoire of cellular functions that are monitored by innate immunity. Here, we summarize several examples in which an innate immune response is triggered when homeostasis of macromolecule in the cell is disrupted in non-infectious or sterile settings. These ever-growing sensing mechanisms expand the repertoire of innate immune recognition, positioning it not only as a key player in host defense but also as a gatekeeper of cellular homeostasis. Therapeutics inspired by these advances to restore cellular homeostasis and correct the immune system could have far-reaching implications.
AID in non-Hodgkin B-cell lymphomas: The consequences of on- and off-target activity.
Leeman-Neill RJ, Bhagat G, Basu U
Adv Immunol · 2024 · PMID 38763700 · Publisher ↗
Activation induced cytidine deaminase (AID) is a key element of the adaptive immune system, required for immunoglobulin isotype switching and affinity maturation of B-cells as they undergo the germinal center (GC) reacti...
Activation induced cytidine deaminase (AID) is a key element of the adaptive immune system, required for immunoglobulin isotype switching and affinity maturation of B-cells as they undergo the germinal center (GC) reaction in peripheral lymphoid tissue. The inherent DNA damaging activity of this enzyme can also have off-target effects in B-cells, producing lymphomagenic chromosomal translocations that are characteristic features of various classes of non-Hodgkin B-cell lymphoma (B-NHL), and generating oncogenic mutations, so-called aberrant somatic hypermutation (aSHM). Additionally, AID has been found to affect gene expression through demethylation as well as altered interactions between gene regulatory elements. These changes have been most thoroughly studied in B-NHL arising from GC B-cells. Here, we describe the most common classes of GC-derived B-NHL and explore the consequences of on- and off-target AID activity in B and plasma cell neoplasms. The relationships between AID expression, including effects of infection and other exposures/agents, mutagenic activity and lymphoma biology are also discussed.
Alternative DNA structures in hematopoiesis and adaptive immunity.
Kligfeld H, Han I, Abraham A … +1 more , Shukla V
Adv Immunol · 2024 · PMID 38763699 · Full text
Besides the canonical B-form, DNA also adopts alternative non-B form conformations which are highly conserved in all domains of life. While extensive research over decades has centered on the genomic functions of B-form...
Besides the canonical B-form, DNA also adopts alternative non-B form conformations which are highly conserved in all domains of life. While extensive research over decades has centered on the genomic functions of B-form DNA, understanding how non-B-form conformations influence functional genomic states remains a fundamental and open question. Recent studies have ascribed alternative DNA conformations such as G-quadruplexes and R-loops as important functional features in eukaryotic genomes. This review delves into the biological importance of alternative DNA structures, with a specific focus on hematopoiesis and adaptive immunity. We discuss the emerging roles of G-quadruplex and R-loop structures, the two most well-studied alternative DNA conformations, in the hematopoietic compartment and present evidence for their functional roles in normal cellular physiology and associated pathologies.
Mechanisms and functions of lncRNAs linked to autoimmune disease risk alleles.
Tian R, Ghosh S
Adv Immunol · 2024 · PMID 38763698 · Publisher ↗
Recent advances in human genomics technologies have helped uncover genetic risk alleles for many complex autoimmune diseases. Intriguingly, over 90% of genome-wide association study (GWAS) risk alleles reside within the...
Recent advances in human genomics technologies have helped uncover genetic risk alleles for many complex autoimmune diseases. Intriguingly, over 90% of genome-wide association study (GWAS) risk alleles reside within the non-coding regions of the genome. An emerging new frontier of functional and mechanistic studies have shed light on the functional relevance of risk alleles that lie within long noncoding RNAs (lncRNAs). Here, we review the mechanisms and functional implications of five evolutionarily conserved lncRNAs that display risk allele association with highly prevalent autoimmune diseases.
Immunometabolism of dendritic cells in health and disease.
Guo C, Chi H
Adv Immunol · 2023 · PMID 38042587 · Full text
Dendritic cells (DCs) are crucial mediators that bridge the innate and adaptive immune responses. Cellular rewiring of metabolism is an emerging regulator of the activation, migration, and functional specialization of DC...
Dendritic cells (DCs) are crucial mediators that bridge the innate and adaptive immune responses. Cellular rewiring of metabolism is an emerging regulator of the activation, migration, and functional specialization of DC subsets in specific microenvironments and immunological conditions. DCs undergo metabolic adaptation to exert immunogenic or tolerogenic effects in different contexts. Also, beyond their intracellular metabolic and signaling roles, metabolites and nutrients mediate the intercellular crosstalk between DCs and other cell types, and such crosstalk orchestrates DC function and immune responses. Here, we provide a comprehensive review of the metabolic regulation of DC biology in various contexts and summarize the current understanding of such regulation in directing immune homeostasis and inflammation, specifically with respect to infections, autoimmunity, tolerance, cancer, metabolic diseases, and crosstalk with gut microbes. Understanding context-specific metabolic alterations in DCs may identify mechanisms for physiological and pathological functions of DCs and yield potential opportunities for therapeutic targeting of DC metabolism in many diseases.
Post-transcriptional regulation of myeloid cell-mediated inflammatory responses.
Liu X, Han W, Hu X
Adv Immunol · 2023 · PMID 38042586 · Publisher ↗
Myeloid cells, particularly macrophages, act as the frontline responders to infectious agents and initiate inflammation. While the molecular mechanisms driving inflammatory responses have primarily focused on pattern rec...
Myeloid cells, particularly macrophages, act as the frontline responders to infectious agents and initiate inflammation. While the molecular mechanisms driving inflammatory responses have primarily focused on pattern recognition by myeloid cells and subsequent transcriptional events, it is crucial to note that post-transcriptional regulation plays a pivotal role in this process. In addition to the transcriptional regulation of innate immune responses, additional layers of intricate network of post-transcriptional mechanisms critically determine the quantity and duration of key inflammatory products and thus the outcome of immune responses. A multitude of mechanisms governing post-transcriptional regulation in innate immunity have been uncovered, encompassing RNA alternative splicing, mRNA stability, and translational regulation. This review encapsulates the current insights into the post-transcriptional regulation of inflammatory genes within myeloid cells, with particular emphasis on translational regulation during inflammation. While acknowledging the advancements, we also shed light on the existing gaps in immunological research pertaining to post-transcriptional levels and propose perspectives that controlling post-transcriptional process may serve as potential targets for therapeutic interventions in inflammatory diseases.
How B cells drive T-cell responses: A key role for cross-presentation of antibody-targeted antigens.
Ossendorp F, Ho NI, Van Montfoort N
Adv Immunol · 2023 · PMID 38042585 · Publisher ↗
In this review we discuss an underexposed mechanism in the adaptive immune system where B cell and T cell immunity collaborate. The main function of B cell immunity is the generation of antibodies which are well known fo...
In this review we discuss an underexposed mechanism in the adaptive immune system where B cell and T cell immunity collaborate. The main function of B cell immunity is the generation of antibodies which are well known for their high affinity and antigen-specificity. Antibodies can bind antigens in soluble form making so-called immune complexes (ICs) or can opsonize antigen-exposing cells or particles for degradation. This leads to well-known effector mechanisms complement activation, antibody-dependent cytotoxicity and phagocytosis. What is less realized is that antibodies can play an important role in the targeting of antigen to dendritic cells (DCs) and thereby can drive T cell immunity. Here we summarize the studies that described this highly efficient process of antibody-mediated antigen uptake in DCs in vitro and in vivo. Only very low doses of antigen can be captured by circulating antibodies and subsequently trapped by DCs in vivo. We studied the handling of these ICs by DCs in subcellular detail. Upon immune complex engulfment DCs can sustain MHC class I and II antigen presentation for many days. Cell biological analysis showed that this function is causally related to intracellular antigen-storage compartments which are functional endolysosomal organelles present in DCs. We speculate that this function is immunologically very important as DCs require time to migrate from the site of infection to the draining lymph nodes to activate T cells. The implications of these findings and the consequences for the immune system, immunotherapy with tumor-specific antibodies and novel vaccination strategies are discussed.
Recent advances in immunopeptidomic-based tumor neoantigen discovery.
Meng W, Schreiber RD, Lichti CF
Adv Immunol · 2023 · PMID 38042584 · Full text
The role of aberrantly expressed proteins in tumors in driving immune-mediated control of cancer has been well documented for more than five decades. Today, we know that both aberrantly expressed normal proteins as well...
The role of aberrantly expressed proteins in tumors in driving immune-mediated control of cancer has been well documented for more than five decades. Today, we know that both aberrantly expressed normal proteins as well as mutant proteins (neoantigens) can function as tumor antigens in both humans and mice. Next-generation sequencing (NGS) and high-resolution mass spectrometry (MS) technologies have made significant advances since the early 2010s, enabling detection of rare but clinically relevant neoantigens recognized by T cells. MS profiling of tumor-specific immunopeptidomes remains the most direct method to identify mutant peptides bound to cellular MHC. However, the need for use of large numbers of cells or significant amounts of tumor tissue to achieve neoantigen detection has historically limited the application of MS. Newer, more sensitive MS technologies have recently demonstrated the capacities to detect neoantigens from fewer cells. Here, we highlight recent advancements in immunopeptidomics-based characterization of tumor-specific neoantigens. Various tumor antigen categories and neoantigen identification approaches are also discussed. Furthermore, we summarize recent reports that achieved successful tumor neoantigen detection by MS using a variety of starting materials, MS acquisition modes, and novel ion mobility devices.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe