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Cover Image
Cover Image
ON THE COVER
Articles by Weigert et al. and Schulz et al. describe two unique ways in which HSP90 inhibition can slow tumor growth. Inhibiting HSP90 opens its clamplike structure and releases and degrades vulnerable client proteins. Image depicts an abstraction of functional HSP90 (green/orange/yellow) in thriving cancer cells and the release of client proteins (blue) after HSP90 inhibition, resulting in cancer cell death. Artwork by Rachel Urkowitz (rachelurk@earthlink.net).
See pages 259 and 275 - PDF Icon PDF LinkTable of Contents
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Perspective
Immunotherapy earns its spot in the ranks of cancer therapy
New results reveal the clinical promise of antitumor immunotherapies, and highlight important considerations for the development and assessment of additional immunotherapeutic modalities.
Review
Targeting glucose metabolism for cancer therapy
Cancer therapeutic targets found within metabolic pathways.
Brief Definitive Report
Pyruvate kinase M2-specific siRNA induces apoptosis and tumor regression
Knockdown of pyruvate kinase M2 induces apoptosis and tumor regression of multiple cancer types.
Identification of modifications in microbial, native tRNA that suppress immunostimulatory activity
2′-O-methylation of guanosine 18 is a naturally occurring tRNA modification that can suppress immune TLR7 responses.
The 2′-O-methylation status of a single guanosine controls transfer RNA–mediated Toll-like receptor 7 activation or inhibition
Bacterial transfer RNA can suppress the immunostimulatory activity of other bacterial tRNAs as a result of the presence of a guanosine modification.
STAT5 is a potent negative regulator of TFH cell differentiation
Interleukin 2, STAT5, and Blimp-1 work together to suppress differentiation of follicular helper T cells in mice.
Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state TH17 cells in the intestine
Homeostatic TH17 differentiation in the intestine is regulated by IL-1β secretion from intestinal macrophages stimulated by commensal microbiota.
Article
Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition
Hsp90 inhibition in B cell acute lymphoblastic leukemia overcomes resistance to JAK2 inhibitors.
Inhibiting the HSP90 chaperone destabilizes macrophage migration inhibitory factor and thereby inhibits breast tumor progression
In several human cancer cell lines, HSP90 inhibitors destabilize macrophage inhibitory factor protein; systemic treatment with an HSP90 inhibitor slows tumor growth and extends overall survival in a mouse model of HER2-positive human breast cancer.
Cernunnos influences human immunoglobulin class switch recombination and may be associated with B cell lymphomagenesis
B cells from Cernunnos-deficient patients contain aberrant class switch recombination junctions, and a dominant-negative Cernunnos mutation was detected in a diffuse large B cell lymphoma sample.
IRE1α activation protects mice against acetaminophen-induced hepatotoxicity
Mice lacking the transcription factor XBP1 exhibit constitutive activation of the stress sensor IRE1α and are protected from acetaminophen overdose–induced acute liver failure.
TNF-induced osteoclastogenesis and inflammatory bone resorption are inhibited by transcription factor RBP-J
The Notch-driven transcription factor RBP-J inhibits osteoclast formation in response to TNF.
Self-reactive human CD4 T cell clones form unusual immunological synapses
Compared with influenza-specific T cells, self-reactive T cells from patients with multiple sclerosis or type 1 diabetes fail to slow down and do not form normal immunological synapses upon encounter with cognate self-peptide presented by MHC.
Sequential class switching is required for the generation of high affinity IgE antibodies
Generation of anaphylaxis-inducing high affinity IgE requires sequential class switching.
Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestine
High-throughput sequencing reveals stability of the intestinal IgA repertoire after plasma cell depletion and changes in repertoire diversity with age and microbial colonization.
Gene expression induced by Toll-like receptors in macrophages requires the transcription factor NFAT5
NFAT5 regulates the induction of TLR-stimulated genes with constitutive binding to the Tnf promoter regardless of TLR ligation and recruitment to Nos2 and Il6 dependent on TLR activation and IKKb.
FoxO1 induces Ikaros splicing to promote immunoglobulin gene recombination
During murine B cell development, PI3 kinase inhibits Ig gene rearrangement by suppressing FoxO1, which mediates Ikaros mRNA splicing; Ikaros is needed for Ig gene recombination.
Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury
Leukocyte recruitment to the kidney during acute injury is mediated by E-selectin–mediated rolling and requires SLP-76 and the adaptor protein ADAP.
