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Advances in Immunology

M N McCracken, R Tavaré, O N Witte, A M Wu
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...
2016: Advances in Immunology
N Sakaguchi, K Maeda
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...
2016: Advances in Immunology
Y Cheng, E W Newell
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...
2016: Advances in Immunology
Y-H Yu, K-I Lin
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...
2016: Advances in Immunology
N Papac-Milicevic, C J-L Busch, C J Binder
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...
2016: Advances in Immunology
Robert D Schreiber
No abstract text is available yet for this article.
2016: Advances in Immunology
James C Yang, Steven A Rosenberg
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...
2016: Advances in Immunology
Matthew D Hellmann, Claire F Friedman, Jedd D Wolchok
T cell checkpoint blockade therapies are revolutionizing the treatment of patients with cancer. Highlighted by the recent success of PD-1 plus CTLA-4 blockade in patients with melanomas, synergistic immunotherapy combinations of modalities represent an important opportunity to improve responses and outcomes for patients. We review the rationale and experience with T cell checkpoint blockade in combination with targeting of other coinhibitory or costimulatory checkpoints, immunomodulatory molecules in the tumor microenvironment, and other anticancer modalities such as vaccines, chemotherapy, and radiation...
2016: Advances in Immunology
Karrie K Wong, WeiWei Aileen Li, David J Mooney, Glenn Dranoff
Therapeutic cancer vaccines aim to induce durable antitumor immunity that is capable of systemic protection against tumor recurrence or metastatic disease. Many approaches to therapeutic cancer vaccines have been explored, with varying levels of success. However, with the exception of Sipuleucel T, an ex vivo dendritic cell vaccine for prostate cancer, no therapeutic cancer vaccine has yet shown clinical efficacy in phase 3 randomized trials. Though disappointing, lessons learned from these studies have suggested new strategies to improve cancer vaccines...
2016: Advances in Immunology
Etienne Becht, Nicolas A Giraldo, Claire Germain, Aurélien de Reyniès, Pierre Laurent-Puig, Jessica Zucman-Rossi, Marie-Caroline Dieu-Nosjean, Catherine Sautès-Fridman, Wolf H Fridman
The outcome of tumors results from genetic and epigenetic modifications of the transformed cells and also from the interactions of the malignant cells with their tumor microenvironment (TME), which includes immune and inflammatory cells. For a given cancer type, the composition of the immunological TME is not homogeneous. Heterogeneity is found between different cancer types and also between tumors from patients with the same type of cancer. Some tumors exhibit a poor infiltration by immune cells, and others are highly infiltrated by lymphocytes...
2016: Advances in Immunology
Stefani Spranger, Ayelet Sivan, Leticia Corrales, Thomas F Gajewski
Despite recent clinical advances in immunotherapy, a fraction of cancer patients fails to respond to these interventions. Evidence from preclinical mouse models as well as clinical samples has provided evidence that the extent of activated T cell infiltration within the tumor microenvironment is associated with clinical response to immunotherapies including checkpoint blockade. Therefore, understanding the molecular mechanisms mediating the lack of T cell infiltration into the tumor microenvironment will be instrumental for the development of new therapeutic strategies to render those patients immunotherapy responsive...
2016: Advances in Immunology
Jeffrey P Ward, Matthew M Gubin, Robert D Schreiber
Definitive experimental evidence from mouse cancer models and strong correlative clinical data gave rise to the Cancer Immunoediting concept that explains the dual host-protective and tumor-promoting actions of immunity on developing cancers. Tumor-specific neoantigens can serve as targets of spontaneously arising adaptive immunity to cancer and thereby determine the ultimate fate of developing tumors. Tumor-specific neoantigens can also function as optimal targets of cancer immunotherapy against established tumors...
2016: Advances in Immunology
Shin Foong Ngiow, Sherene Loi, David Thomas, Mark J Smyth
Immunotherapy is now evolving into a major therapeutic option for cancer patients. Such clinical advances also promote massive interest in the search for novel immunotherapy targets, and to understand the mechanism of action of current drugs. It is projected that a series of novel immunotherapy agents will be developed and assessed for their therapeutic activity. In light of this, in vivo experimental mouse models that recapitulate human malignancies serve as valuable tools to validate the efficacy and safety profile of immunotherapy agents, before their transition into clinical trials...
2016: Advances in Immunology
Huai-Chia Chuang, Xiaohong Wang, Tse-Hua Tan
MAP kinase kinase kinase kinases (MAP4Ks) belong to the mammalian Ste20-like family of serine/threonine kinases. MAP4Ks including MAP4K1/HPK1, MAP4K2/GCK, MAP4K3/GLK, MAP4K4/HGK, MAP4K5/KHS, and MAP4K6/MINK have been reported to induce JNK activation through activating the MAP3K-MAP2K cascade. The physiological roles of MAP4Ks in immunity and inflammation are largely unknown until recent studies using biochemical approaches and knockout mice. Surprisingly, JNK is not the major target of MAP4Ks in immune cells; MAP4Ks regulate immune responses through novel targets...
2016: Advances in Immunology
Luis J Sigal
Ectromelia virus is a mouse-specific orthopoxvirus that, following footpad infection or natural transmission, causes mousepox in most strains of mice, while a few strains, such as C57BL/6, are resistant to the disease but not to the infection. Mousepox is an acute, systemic, highly lethal disease of remarkable semblance to smallpox, caused by the human-specific variola virus. Starting in 1929 with its discovery by Marchal, work with ECTV has provided essential information for our current understanding on how viruses spread lympho-hematogenously, the genetic control of antiviral resistance, the role of different components of the innate and adaptive immune system in the control of primary and secondary infections with acute viruses, and how the mechanisms of immune evasion deployed by the virus affect virulence in vivo...
2016: Advances in Immunology
Takehiko Sasazuki, Hidetoshi Inoko, Satoko Morishima, Yasuo Morishima
The human leukocyte antigen (HLA) genomic region spanning about 4 Mb is the most gene dense and the polymorphic stretches in the human genome. A total of the 269 loci were identified, including 145 protein coding genes mostly important for immunity and 50 noncoding RNAs (ncRNAs). Biological function of these ncRNAs remains unknown, becoming hot spot in the studies of HLA-associated diseases. The genomic diversity analysis in the HLA region facilitated by next-generation sequencing will pave the way to molecular understanding of linkage disequilibrium structure, population diversity, histocompatibility in transplantation, and associations with autoimmune diseases...
2016: Advances in Immunology
Ellen V Rothenberg, Jonas Ungerbäck, Ameya Champhekar
T-lymphocyte development branches off from other lymphoid developmental programs through its requirement for sustained environmental signals through the Notch pathway. In the thymus, Notch signaling induces a succession of T-lineage regulatory factors that collectively create the T-cell identity through distinct steps. This process involves both the staged activation of T-cell identity genes and the staged repression of progenitor-cell-inherited regulatory genes once their roles in self-renewal and population expansion are no longer needed...
2016: Advances in Immunology
Armstrong Murira, Pascal Lapierre, Alain Lamarre
Similar to human immunodeficiency virus (HIV)-1, vaccine-induced elicitation of broadly neutralizing (bNt) antibodies (Abs) is gaining traction as a key goal toward the eradication of the hepatitis C virus (HCV) pandemic. Previously, the significance of the Ab response against HCV was underappreciated given the prevailing evidence advancing the role of the cellular immune response in clearance and overall control of the infection. However, recent findings have driven growing interest in the humoral arm of the immune response and in particular the role of bNt responses due to their ability to confer protective immunity upon passive transfer in animal models...
2016: Advances in Immunology
Marie-Dominique Filippi
The neutrophil transmigration across the blood endothelial cell barrier represents the prerequisite step of innate inflammation. Neutrophil recruitment to inflamed tissues occurs in a well-defined stepwise manner, which includes elements of neutrophil rolling, firm adhesion, and crawling onto the endothelial cell surface before transmigrating across the endothelial barrier. This latter step known as diapedesis can occur at the endothelial cell junction (paracellular) or directly through the endothelial cell body (transcellular)...
2016: Advances in Immunology
Hisashi Arase
Misfolded proteins localized in the endoplasmic reticulum are degraded promptly and thus are not transported outside cells. However, misfolded proteins in the endoplasmic reticulum are rescued from protein degradation upon association with major histocompatibility complex (MHC) class II molecules and are transported to the cell surface by MHC class II molecules without being processed to peptides. Studies on the misfolded proteins rescued by MHC class II molecules have revealed that misfolded proteins associated with MHC class II molecules are specific targets for autoantibodies produced in autoimmune diseases...
2016: Advances in Immunology
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