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Cold Spring Harbor Perspectives in Biology

Adam M Heck, Jeffrey Wilusz
RNA decay plays a major role in regulating gene expression and is tightly networked with other aspects of gene expression to effectively coordinate post-transcriptional regulation. The goal of this work is to provide an overview of the major factors and pathways of general messenger RNA (mRNA) decay in eukaryotic cells, and then discuss the effective interplay of this cytoplasmic process with the protein synthesis machinery. Given the transcript-specific and fluid nature of mRNA stability in response to changing cellular conditions, understanding the fundamental networking between RNA decay and translation will provide a foundation for a complete mechanistic understanding of this important aspect of cell biology...
January 8, 2018: Cold Spring Harbor Perspectives in Biology
Marcelo B Sztein
Although induction of CD8+ responses is widely accepted as critical in clearing viral infections and necessary for effective vaccines against viruses, much less is known regarding the role of these cells in bacterial and other infections, particularly those that enter the host via the gastrointestinal tract. In this commentary, I discuss the likelihood that CD8+ responses are also important in protection from intestinal Gram-negative bacteria, as well as the many factors that should be taken into consideration during the development of vaccines, based on eliciting long-term protection predominantly mediated by CD8+ responses against these organisms...
December 18, 2017: Cold Spring Harbor Perspectives in Biology
Lalit K Beura, Stephen C Jameson, David Masopust
Although CD8 T-cell vaccines do not have the record of success of humoral-mediated vaccines, they do not receive the same degree of effort. Many diseases, including malaria, tuberculosis, and acquired immune deficiency syndrome (AIDS) have not yielded to vaccines, and intrinsic barriers may impede approaches limited solely to generating antibodies. Moreover, population growth and modernization are driving an increased pace of new emerging global health threats (human immunodeficiency virus [HIV] is a recent example), which will create unpredictable challenges for vaccinologists...
December 18, 2017: Cold Spring Harbor Perspectives in Biology
Haydn T Kissick
Recent work by several groups has undoubtedly shown that we can produce cancer vaccines targeting neoantigens. However, each vaccine is essentially a single-use, patient-specific product, making this approach resource-intensive. For this reason, it is important to ask whether this approach will be any more successful than what has been attempted during the last 30 years using vaccines targeting self-epitopes. Here, we discuss what might be expected from neoantigen vaccines based on our experience in chronic viral infections, and how this new approach may be applied to cancer immunotherapy...
December 18, 2017: Cold Spring Harbor Perspectives in Biology
Olivera J Finn, Hans-Georg Rammensee
The term "neoantigen," as applied to molecules newly expressed on tumor cells, has a long history. The groundbreaking discovery of a cancer causing virus in chickens by Rous over 100 years ago, followed by discoveries of other tumor-causing viruses in animals, suggested a viral etiology of human cancers. The search for other oncogenic viruses in the 1960s and 1970s resulted in the discoveries of Epstein-Barr virus (EBV), hepatitis B virus (HBV), and human papilloma virus (HPV), and continues until the present time...
December 18, 2017: Cold Spring Harbor Perspectives in Biology
Joseph C Sun, Lewis L Lanier
Immunological memory is an evolutionary adaptation of the vertebrate immune system that protects the host from repeated pathogen infection. T and B cells possess the specificity and longevity required to generate immune memory, whereas natural killer (NK) cells make up a component of the immune system that was not thought to possess these features. However, much evidence from the last decade has challenged this dogma. The investigators were asked to address the following questions: Is there NK cell memory? And can NK cell memory be harnessed for vaccination? Thus, this article explores the recent literature showing immune memory in NK cells...
December 18, 2017: Cold Spring Harbor Perspectives in Biology
Harold R Neely, Irina B Mazo, Carmen Gerlach, Ulrich H von Andrian
Natural killer (NK) cells have historically been considered to be a part of the innate immune system, exerting a rapid response against pathogens and tumors in an antigen (Ag)-independent manner. However, over the past decade, evidence has accumulated suggesting that at least some NK cells display certain characteristics of adaptive immune cells. Indeed, NK cells can learn and remember encounters with a variety of Ags, including chemical haptens and viruses. Upon rechallenge, memory NK cells mount potent recall responses selectively to those Ags...
December 18, 2017: Cold Spring Harbor Perspectives in Biology
Andrew J McMichael
Vaccines that stimulate CD8+ T cells could clear early virus infection or control ongoing infection and prevent disease. This could be valuable to combat human immunodeficiency virus type 1 (HIV-1) where it has not yet been possible to generate broadly reacting neutralizing antibodies with a vaccine. However, HIV-1 vaccines aimed at stimulating CD8+ T cells have had no success. In contrast, a cytomegalovirus vectored simian immunodeficiency virus (SIV) vaccine enabled clearance of early SIV infection. This may open the door to the design of an effective HIV vaccine...
December 18, 2017: Cold Spring Harbor Perspectives in Biology
Megan A Cooper, Todd A Fehniger, Marco Colonna
Studies over the last decade have decisively shown that innate immune natural killer (NK) cells exhibit enhanced long-lasting functional responses following a single activation event. With the increased recognition of memory and memory-like properties of NK cells, questions have arisen with regard to their ability to effectively mediate vaccination responses in humans. Moreover, recently discovered innate lymphoid cells (ILCs) could also potentially exhibit memory-like functions. Here, we review different forms of NK cell memory, and speculate about the ability of these cells and ILCs to meaningfully contribute to vaccination responses...
December 18, 2017: Cold Spring Harbor Perspectives in Biology
Christine A Biron, Marcus Altfeld
Natural killer (NK) cells are components of innate immunity mediating defense at early times after viral infections. Their cytokine production and cell-mediated cytotoxicity functions overlap those of CD8 T cells elicited later during primary adaptive immune responses, but the populations are distinguished by their basal states and activating receptors as well as the kinetics of their responses. Demonstration of long-lived NK cells has led to speculation on the potential for inducing these to contribute to immunological memory...
December 18, 2017: Cold Spring Harbor Perspectives in Biology
Stephen P Schoenberger
Recent advances in genomic sequencing and bioinformatics have empowered a revolution in immuno-oncology that has led to numerous unambiguous demonstrations of spontaneous and therapy-induced T-cell responses in patients against a subset of immunogenic tumor-specific somatic mutations known as neoantigens. These findings raise the exciting possibility that patients could be therapeutically treated with personalized vaccines against the mutations expressed by their own tumor. A central challenge for the broader clinical application of this approach will be to define the best antigens to target, to determine the subset of patients most likely to derive significant clinical benefit, and, finally, to discover both the best method of vaccine delivery and the optimal time in the disease course to do so...
December 18, 2017: Cold Spring Harbor Perspectives in Biology
Maho Nagasawa, Hergen Spits, Xavier Romero Ros
Innate lymphoid cells (ILCs) have emerged as an expanding family of effector cells particularly enriched in the mucosal barriers. ILCs are promptly activated by stress signals and multiple epithelial- and myeloid-cell-derived cytokines. In response, ILCs rapidly secrete effector cytokines, which allow them to survey and maintain the mucosal integrity. Uncontrolled action of ILCs might contribute to tissue damage, chronic inflammation, metabolic diseases, autoimmunity, and cancer. Here we discuss the recent advances in our understanding of the cytokine network that modulate ILC immune responses: stimulating cytokines, signature cytokines secreted by ILC subsets, autocrine cytokines, and cytokines that induce cell plasticity...
December 11, 2017: Cold Spring Harbor Perspectives in Biology
Thomas A Waldmann
Cytokines that control the immune response were shown to have efficacy in preclinical murine cancer models. Interferon (IFN)-α is approved for treatment of hairy cell leukemia, and interleukin (IL)-2 for the treatment of advanced melanoma and metastatic renal cancer. In addition, IL-12, IL-15, IL-21, and granulocyte macrophage colony-stimulating factor (GM-CSF) have been evaluated in clinical trials. However, the cytokines as monotherapy have not fulfilled their early promise because cytokines administered parenterally do not achieve sufficient concentrations in the tumor, are often associated with severe toxicities, and induce humoral or cellular checkpoints...
November 3, 2017: Cold Spring Harbor Perspectives in Biology
Ajithkumar Vasanthakumar, Axel Kallies
Cytokines play an integral role in shaping innate and adaptive immune responses. Members of the interleukin (IL)-1 family regulate a plethora of immune-cell-mediated processes, which include pathogen defense and tissue homeostasis. Notably, the IL-1 family cytokine IL-33 promotes adaptive and innate type 2 immune responses, confers viral protection and facilitates glucose metabolism and tissue repair. At the cellular level, IL-33 stimulates differentiation, maintenance, and function of various immune cell types, including regulatory T cells, effector CD4+ and CD8+ T cells, macrophages, and type 2 innate lymphoid cells (ILC2s)...
November 3, 2017: Cold Spring Harbor Perspectives in Biology
Masao Hashimoto, Se Jin Im, Koichi Araki, Rafi Ahmed
The common γ-chain cytokines, interleukin (IL)-2, IL-7, and IL-15, regulate critical aspects of antiviral CD8 T-cell responses. During acute infections, IL-2 controls expansion and differentiation of antiviral CD8 T cells, whereas IL-7 and IL-15 are key cytokines to maintain memory CD8 T cells long term in an antigen-independent manner. On the other hand, during chronic infections, in which T-cell exhaustion is established, precise roles of these cytokines in regulation of antiviral CD8 T-cell responses are not well defined...
November 3, 2017: Cold Spring Harbor Perspectives in Biology
Tatyana Svitkina
SUMMARYThe actin cytoskeleton-a collection of actin filaments with their accessory and regulatory proteins-is the primary force-generating machinery in the cell. It can produce pushing (protrusive) forces through coordinated polymerization of multiple actin filaments or pulling (contractile) forces through sliding actin filaments along bipolar filaments of myosin II. Both force types are particularly important for whole-cell migration, but they also define and change the cell shape and mechanical properties of the cell surface, drive the intracellular motility and morphogenesis of membrane organelles, and allow cells to form adhesions with each other and with the extracellular matrix...
January 2, 2018: Cold Spring Harbor Perspectives in Biology
John E Spiro
Scientists who leave the laboratory bench to work for biomedical foundations mobilize and focus resources on the most promising research behind a foundation's mission. They acquire a broad view of a field, interact closely with research scientists at meetings and laboratory visits, and often manage proposal review boards and monitor grant progress. Increasingly, scientists at foundations also have a more active role in catalyzing research: They are involved in organizing targeted workshops, setting research priorities, and directly creating and managing resources for a scientific community...
December 1, 2017: Cold Spring Harbor Perspectives in Biology
Elly M Hol, Yassemi Capetanaki
SummaryType III intermediate filament (IF) proteins assemble into cytoplasmic homopolymeric and heteropolymeric filaments with other type III and some type IV IFs. These highly dynamic structures form an integral component of the cytoskeleton of muscle, brain, and mesenchymal cells. Here, we review the current ideas on the role of type III IFs in health and disease. It turns out that they not only offer resilience to mechanical strains, but, most importantly, they facilitate very efficiently the integration of cell structure and function, thus providing the necessary scaffolds for optimal cellular responses upon biochemical stresses and protecting against cell death, disease, and aging...
December 1, 2017: Cold Spring Harbor Perspectives in Biology
Susan Froshauer
The world of biotechnology "start-ups" and entrepreneurship offers exciting new avenues for driving state-of-the-art research using an arsenal of multidisciplinary skills, whether your role is as part of a team or as a leader. Although traditionally these positions may not be as secure as those offered by some of the larger companies, the small start-up culture provides opportunities for contributing at many levels to a wide range of responsibilities: from scientific discovery to delivery of proof of concept and intellectual property; from analysis of market opportunities and competitive intelligence to creation of time lines and business plans for a first product...
November 1, 2017: Cold Spring Harbor Perspectives in Biology
Adrian F Pegoraro, Paul Janmey, David A Weitz
SUMMARYThe cytoskeleton is the major mechanical structure of the cell; it is a complex, dynamic biopolymer network comprising microtubules, actin, and intermediate filaments. Both the individual filaments and the entire network are not simple elastic solids but are instead highly nonlinear structures. Appreciating the mechanics of biopolymer networks is key to understanding the mechanics of cells. Here, we review the mechanical properties of cytoskeletal polymers and discuss the implications for the behavior of cells...
November 1, 2017: Cold Spring Harbor Perspectives in Biology
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