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Current Opinion in Immunology

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https://www.readbyqxmd.com/read/28208102/oncogenic-growth-factor-signaling-mediating-tumor-escape-from-cellular-immunity
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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/27907816/nucleic-acid-sensing-tlrs-trafficking-and-regulation
#12
REVIEW
Olivia Majer, Bo Liu, Gregory M Barton
Toll-like receptors (TLRs) play an important role in innate immune responses against pathogenic microorganisms or tissue damage. Nucleic acid (NA)-sensing TLRs localize in intracellular vesicular compartments and recognize foreign-derived and host-derived nucleic acid ligands. Inappropriate activation of NA-sensing TLRs can cause pathogenic inflammation and autoimmunity. Multiple regulatory mechanisms exist to limit recognition of self-NAs. This review summarizes recent progress that has been made in understanding how NA-sensing TLRs are regulated via trafficking, proteolytic cleavage, as well as ligand processing and recognition...
November 28, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27821272/targeting-cytokine-signaling-in-autoimmunity-back-to-the-future-and-beyond
#13
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
#14
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
https://www.readbyqxmd.com/read/27744240/t-cell-exhaustion-and-immune-mediated-disease-the-potential-for-therapeutic-exhaustion
#15
REVIEW
Eoin F McKinney, Kenneth Gc Smith
T cell exhaustion represents a continuous spectrum of cellular dysfunction induced during chronic viral infection, facilitating viral persistence and associating with poor clinical outcome. Modulation of T cell exhaustion can restore function in exhausted CD8 T cells, promoting viral clearance. Exhaustion has also been implicated as playing an important role in anti-tumour responses, whereby exhausted tumour-infiltrating lymphocytes fail to control tumour progression. More recently exhaustion has been linked to long-term clinical outcome in multiple autoimmune diseases but, in contrast to cancer or infection, it is associated with a favourable clinical outcome characterised by fewer relapses...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27718448/endoplasmic-reticulum-stress-in-beta-cells-and-autoimmune-diabetes
#16
REVIEW
Amy L Clark, Fumihiko Urano
Type 1 diabetes results from the autoimmune destruction of pancreatic β cells, leading to insulin deficiency and hyperglycemia. Although multiple attempts have been made to slow the autoimmune process using immunosuppressive or immunomodulatory agents, there are still no effective treatments that can delay or reverse the progression of type 1 diabetes in humans. Recent studies support endoplasmic reticulum (ER) as a novel target for preventing the initiation of the autoimmune reaction, propagation of inflammation, and β cell death in type 1 diabetes...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27718447/targeting-b-cells-in-treatment-of-autoimmunity
#17
REVIEW
S Elizabeth Franks, Andrew Getahun, P Mark Hogarth, John C Cambier
B cells have emerged as effective targets for therapeutic intervention in autoimmunities in which the ultimate effectors are antibodies, as well as those in which T cells are primary drivers of inflammation. Proof of this principle has come primarily from studies of the efficacy of Rituximab, an anti-CD20 mAb that depletes B cells, in various autoimmune settings. These successes have inspired efforts to develop more effective anti-CD20s tailored for specific needs, as well as biologicals and small molecules that suppress B cell function without the risks inherent in B cell depletion...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27710840/macrophages-and-dendritic-cells-in-islets-of-langerhans-in-diabetic-autoimmunity-a-lesson-on-cell-interactions-in-a-mini-organ
#18
REVIEW
Javier A Carrero, Stephen T Ferris, Emil R Unanue
Islets of Langerhans of all species harbor a small number of resident macrophages. These macrophages are found since birth, do not exchange with blood monocytes, and are maintained by a low level of replication. Under steady state conditions, the islet macrophages are in an activated state. Islet macrophages have an important homeostatic role in islet physiology. At the start of the autoimmune process in the NOD mouse, a small number of CD103+ dendritic cells (DC) are found at about the same time that CD4+ T cells also appear in islets...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27710839/environmental-control-of-autoimmune-inflammation-in-the-central-nervous-system
#19
REVIEW
Veit Rothhammer, Francisco J Quintana
Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disorder of the central nervous system (CNS), which causes severe disability and requires extensive medical attention and treatment. While the infiltration of pathogenic immune cells into the CNS leads to the formation of inflammatory lesions in its initial relapsing-remitting stage, late stages of MS are characterized by progressive neuronal loss and demyelination even without continued interaction with the peripheral immune compartment...
December 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27636649/t-cells-in-systemic-lupus-erythematosus
#20
REVIEW
Abel Suárez-Fueyo, Sean J Bradley, George C Tsokos
Systemic Lupus Erythematosus is an autoimmune disorder caused by a complex combination of genetic, epigenetic and environmental factors. Different polymorphisms and epigenetic modifications lead to altered gene expression and function of several molecules which lead to abnormal T cell responses. Metabolic and functional alterations result in peripheral tolerance failures and biased differentiation of T cells into pro-inflammatory and B cell-helper phenotypes as well as the accumulation of disease-promoting memory T cells...
December 2016: Current Opinion in Immunology
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