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Current Opinion in Immunology

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https://www.readbyqxmd.com/read/28319730/deconstructing-the-germinal-center-one-cell-at-a-time
#1
REVIEW
Chad R Dufaud, Louise J McHeyzer-Williams, Michael G McHeyzer-Williams
Successful vaccination relies on driving the immune response towards high specificity, affinity and longevity. Germinal centers facilitate the evolution of antigen-specific B cells by iterative rounds of diversification, selection, and differentiation to memory and plasma cells. Experimental evidence points to B cell receptor affinity and amount of antigen presented to follicular helper T cells as main drivers of clonal evolution. Concurrent studies suggest that modifiers of cognate contact, temporal mechanisms, and stochastic factors can also shape diversity and influence differentiation to memory and plasma cells, but molecular pathways driving these selection decisions are unresolved...
March 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319729/stromal-networking-cellular-connections-in-the-germinal-centre
#2
REVIEW
Alice E Denton, Michelle A Linterman
Secondary lymphoid organs are organized into distinct zones, governed by different types of mesenchymal stromal cells. These stromal cell subsets are critical for the generation of protective humoral immunity because they direct the migration of, and interaction between, multiple immune cell types to form the germinal centre. The germinal centre response generates long-lived antibody-secreting plasma cells and memory B cells which can provide long-term protection against re-infection. Stromal cell subsets mediate this response through control of immune cell trafficking, activation, localization and antigen access within the secondary lymphoid organ...
March 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319733/plasma-cell-and-memory-b-cell-differentiation-from-the-germinal-center
#3
REVIEW
Dan Suan, Christopher Sundling, Robert Brink
Germinal centers (GCs) form in secondary lymphoid tissues in response to antigenic challenge and are the site of somatic hypermutation, generating GC B cells with increasing affinity for the inciting agent that are positively selected over time. However, it is not until GC B cells differentiate into memory B cells and plasma cells and egress from the GC back into the circulation that effective long-lived humoral immunity is conferred upon the host. Here we review what is known about the signals that initiate the transition from a GC B cell into the memory B cell and plasma cell compartments and the downstream transcriptional regulation of these processes...
March 16, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319732/an-antigen-to-remember-regulation-of-b-cell-memory-in-health-and-disease
#4
REVIEW
Aleta Pupovac, Kim L Good-Jacobson
Vaccine success relies on the formation of immunity. Humoral immunity is critical and is mediated by long-lived antibody-secreting cells and memory B cells (MBCs). Chronic infectious diseases cause a significant global burden of disease; pathogens that evade the immune system can cause phenotypical and functional changes to immune memory populations. Thus, recent studies have focused on MBC subset function. IgM(+) MBCs have emerged as important early responders in malaria. Atypical MBCs have functional qualities associated with exhaustion in chronic infectious diseases, but the requirements for their formation and where they localize remains unknown...
March 16, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319731/stimulating-cd27-to-quantitatively-and-qualitatively-shape-adaptive-immunity-to-cancer
#5
REVIEW
Timothy Nj Bullock
The capacity of the immune system to recognize and respond to tumors has been appreciated for over 100 years. However, clinical success has largely depended on the elucidation of the positive and negative regulators of effector cells after their activation via the antigen cell receptor. On the one hand, effector cells upregulate checkpoint molecules that are thought to play a role in limiting immunopathology. On the other, second and third waves of costimulation are often required to promote the expansion, survival and differentiation of effector cells...
March 16, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28236750/targeting-nk-cell-checkpoints-for-cancer-immunotherapy
#6
REVIEW
Aura Muntasell, Maria C Ochoa, Luna Cordeiro, Pedro Berraondo, Ascension López-Díaz de Cerio, Mariona Cabo, Miguel López-Botet, Ignacio Melero
Natural Killer (NK) cells are cytotoxic lymphocytes specialized in early defense against virus-infected and transformed cells. NK-cell function is regulated by activating and inhibitory surface receptors recognizing their ligands on transformed cells. Modulation of NK numbers and/or function by a variety of agents such as cytokines and monoclonal antibodies may result in enhanced anti-tumor activity. Recombinant cytokines (i.e., IL-15 and IL-2), antibodies blocking inhibitory receptors (i.e., KIR, NKG2A and TIGIT) and agonists delivering signals via CD137, NKG2D and CD16 stand out as the most suitable opportunities...
February 22, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28222333/immunoprofiling-as-a-predictor-of-patient-s-response-to-cancer-therapy-promises-and-challenges
#7
REVIEW
Daniel Bethmann, Zipei Feng, Bernard A Fox
Immune cell infiltration is common to many tumors and has been recognized by pathologists for more than 100 years. The application of digital imaging and objective assessment software allowed a concise determination of the type and quantity of immune cells and their location relative to the tumor and, in the case of colon cancer, characterized overall survival better than AJCC TNM staging. Subsequently, expression of PD-L1, by 50% or more tumor cells, identified NSCLC patients with double the response rate to anti-PD-1...
February 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28208102/oncogenic-growth-factor-signaling-mediating-tumor-escape-from-cellular-immunity
#8
REVIEW
Fernando Concha-Benavente, Robert L Ferris
Unrestrained growth factor signals can promote carcinogenesis, as well as other hallmarks of cancer such as immune evasion. Our understanding of the function and complex regulation of HER family of receptors has led to the development of targeted therapeutic agents that suppress tumor growth. However, these receptors also mediate escape from recognition by the host immune system. We discuss how HER family of oncogenic receptors downregulate tumor antigen presentation and upregulate suppressive membrane-bound or soluble secreted inhibitory molecules that ultimately lead to impaired cellular immunity mediated by cytotoxic T lymphocyte (CTL) recognition...
February 13, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28192720/dendritic-cells-in-cancer-the-role-revisited
#9
REVIEW
Filippo Veglia, Dmitry I Gabrilovich
Dendritic cells (DCs) with their potent antigen presenting ability are long considered as critical factor in antitumor immunity. Despite high potential in promoting antitumor responses, tumor-associated DCs are largely defective in their functional activity and can contribute to immune suppression in cancer. In recent years existence of immune suppressive regulatory DCs in tumor microenvironment was described. Monocytic myeloid derived suppressor cells (M-MDSCs) can contribute to the pool of tumor associated DCs by differentiating to inflammatory DCs (inf-DCs), which appear to have specific phenotype and is critical component of antitumor response...
February 10, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28189879/immune-checkpoint-receptors-in-cancer-redundant-by-design
#10
REVIEW
Jing Li, Ling Ni, Chen Dong
Co-inhibitory receptors expressed on activated immune cells function to regulate T cell tolerance to self-antigens, also serving by tumor cells to escape from eradication by the host immune system. Therefore, blockade of immune checkpoint receptors (ICR) has become a promising immunotherapeutic strategy for treatment of a wide variety of cancers. However, blockade of one of the immune checkpoint receptors alone is often not sufficiently effective; co-blockade shows synergic effects in reversing immunosuppression...
February 9, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28160624/murine-models-of-germinal-center-derived-lymphomas
#11
REVIEW
Parham Ramezani-Rad, Robert C Rickert
The germinal center (GC) reaction is an adaptive immune response to select B cells bearing high-affinity B cell receptors (BCRs) to undergo further differentiation into antibody-producing cells or memory B cells. To drive affinity maturation, (GC) B cells undergo rounds of hypermutation and rapid proliferation, which can enhance susceptibility to malignant transformation. Lymphomas frequently originate from GC B cells, but the etiology for most lymphoma subtypes is unknown. Work in the past decade has more fully documented the mutational landscape in lymphomas, but the impact of these genomic lesions is often difficult to ascertain...
February 1, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28103497/host-microbiota-interactions-epigenomic-regulation
#12
REVIEW
Vivienne Woo, Theresa Alenghat
The coevolution of mammalian hosts and their commensal microbiota has led to the development of complex symbiotic relationships between resident microbes and mammalian cells. Epigenomic modifications enable host cells to alter gene expression without modifying the genetic code, and therefore represent potent mechanisms by which mammalian cells can transcriptionally respond, transiently or stably, to environmental cues. Advances in genome-wide approaches are accelerating our appreciation of microbial influences on host physiology, and increasing evidence highlights that epigenomics represent a level of regulation by which the host integrates and responds to microbial signals...
January 16, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28088708/germinal-centers-programmed-for-affinity-maturation-and-antibody-diversification
#13
REVIEW
Oliver Bannard, Jason G Cyster
The seminal discovery by Eisen that antibodies undergo improvements in antigen-binding affinity over the course of an immune response led to a long running search for the underlying mechanism. Germinal centers in lymphoid organs are now recognized to be critically involved in this phenomenon, known as antibody affinity maturation. As well as improving in affinity for specific epitopes, some antibody responses maintain or even increase their breadth of antigen-recognition over time. This has led to another intense line of research aimed at understanding how broadly neutralizing anti-pathogen responses are generated...
January 12, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28088707/dna-sensing-and-immune-responses-in-cancer-therapy
#14
REVIEW
Jian Qiao, Haidong Tang, Yang-Xin Fu
The identification of critical DNA sensors and their pathways has led to revealing the central role of DNA sensing in immune system. It has been initially demonstrated that DNA sensing and immune responses have high impacts on the development and prevention of infection and inflammatory. In addition to toll-like receptor pathways, there is now also emerging evidence that cytosolic enzyme cyclic GMP-AMP synthase (cGAS) is essential for the recognition of not only pathogen-derived DNA but also tumor DNA for innate sensing...
January 12, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28088061/galectins-emerging-regulatory-checkpoints-linking-tumor-immunity-and-angiogenesis
#15
REVIEW
Santiago P Méndez-Huergo, Ada G Blidner, Gabriel A Rabinovich
Immune checkpoints, a plethora of inhibitory pathways aimed at maintaining immune cell homeostasis, may be co-opted by cancer cells to evade immune destruction. Therapies targeting immune checkpoints have reached a momentum yielding significant clinical benefits in patients with various malignancies by unleashing anti-tumor immunity. Galectins, a family of glycan-binding proteins, have emerged as novel regulatory checkpoints that promote immune evasive programs by inducing T-cell exhaustion, limiting T-cell survival, favoring expansion of regulatory T cells, de-activating natural killer cells and polarizing myeloid cells toward an immunosuppressive phenotype...
January 11, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27984782/nk-cells-in-host-responses-to-viral-infections
#16
REVIEW
Viola C Lam, Lewis L Lanier
Natural killer (NK) cells are cytotoxic innate lymphocytes that play an important role in viral clearance. NK cell responses to viral infections were originally believed to be non-specific and lacked immune memory recall responses. It is now appreciated that NK cell responses to viral infections can be specific and in some cases memory recall responses are established. Increasing evidence also illuminates the complexity of NK cell interactions with both innate and adaptive immune cells. Here, we summarize the evidence for NK cell-specific memory responses to viral infections and the intricate reciprocal interactions between NK cells and other immune cells that dictate their activation and effector functions...
December 13, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27951434/neutrophil-migration-in-inflammation-intercellular-signal-relay-and-crosstalk
#17
REVIEW
Sioh-Yang Tan, Wolfgang Weninger
Neutrophils are innate effector cells armed with a potent machinery to combat damage and infection within tissues. Their ability to rapidly respond to danger signals and mobilise is crucial to their role. After extravasation, neutrophil populations often exhibit swarming behaviour. Swarming occurs in distinct phases and is coordinated via inter-neutrophil signal relay in the form of small molecule mediators. Neutrophils also engage in multi-dimensional crosstalk with tissue-resident cells and incoming leukocytes in the inflammatory milieu...
December 9, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27940327/peptide-vaccines-in-cancer-old-concept-revisited
#18
REVIEW
Takumi Kumai, Hiroya Kobayashi, Yasuaki Harabuchi, Esteban Celis
Synthetic peptide vaccines aim to elicit and expand tumor-specific T cells capable of controlling or eradicating the tumor. Despite the high expectations based on preclinical studies, the results of clinical trials using peptide vaccines have been disappointing. Thus, many researchers in the field have considered peptide vaccines as outdated and no longer viable for cancer therapy. However, recent progress in understanding the critical roles of immune adjuvants, modes of vaccine administration and T cell dynamics has lead to a rebirth of this approach and reconsidering the use of peptide vaccines for treating malignant disorders...
December 8, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27821272/targeting-cytokine-signaling-in-autoimmunity-back-to-the-future-and-beyond
#19
REVIEW
Kiyoshi Hirahara, Daniella Schwartz, Massimo Gadina, Yuka Kanno, John J O'Shea
Cytokines represent structurally diverse soluble factors with critical roles in normal immune function and the pathogenesis of autoimmunity. The emergence of many successful biological therapies targeting cytokines and cytokine receptors exemplifies the importance of cytokines in driving human autoimmune disease; unsurprisingly, there is no paucity of reviews on this subject. Nonetheless, many patients with autoimmune disease do not respond to biologicals, and cure remains an unmet goal. Thus, targeting the intracellular pathways employed by cytokines provides new therapeutic opportunities...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27764715/understanding-mechanisms-of-autoimmunity-through-translational-research-in-vitiligo
#20
REVIEW
James P Strassner, John E Harris
Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells...
December 2016: Current Opinion in Immunology
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