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Two new studies demonstrate that so-called 'liquid biopsies' may reveal important genomic information needed to monitor treatment responses, forecast tumor recurrences, and provide a rationale for novel therapeutic strategies in patients with lung cancer and colon cancer.
In the liver there is a fine balance between immune surveillance of blood-borne infections and regulation of immunopathology. A new study identifies a role for granulocytic myeloid-derived suppressor cells in limiting T cell–mediated immunopathology in hepatitis B virus infection.
Atherosclerosis is the primary cause of heart attacks and strokes and is caused by a chronic inflammatory response in the coronary and carotid arteries. A new study shows that smooth muscle cells within atherosclerotic plaques can change phenotypes to become macrophage-like cells, thereby revealing the remarkable plasticity of these cells.
Tissue-resident memory T cells (TRM cells) protect against recurrent or renewed infection in barrier tissues such as skin and mucosa. A new study sheds light on the clonal origin of TRM cells and demonstrates a crucial role for tissue-embedded T cell memory in contact hypersensitivity in skin.
A new study identifies recurrent mutations in the purine biosynthesis gene phosphoribosyl pyrophosphate synthetase 1 (PRPS1) in relapsed acute lymphoblastic leukemia (ALL). This work highlights the importance of this pathway in the pathogenesis of relapse and suggests an approach to predicting and circumventing resistance in ALL.
To target and kill cancer cells, oncolytic viruses exploit signaling pathways that promote tumor growth. A new study shows that the cancer stromal fibroblast factor FGF2 is a crucial component of a tumor–TGF-β axis that renders cancer cells sensitive to virus infection.
Neuropathic pain is a debilitating condition affecting millions of people worldwide. A new study investigates mechanisms of neuropathic pain initiation and identifies a promising therapeutic currently used for acute respiratory distress syndrome that may also limit acute neuropathic pain.
The maintenance of blood glucose involves the coordination of multiple organ systems. Two new studies indicate that metformin and resveratrol activate metabolic sensors in the duodenum and initiate a neural loop that reduces liver glucose production in rat models of type 2 diabetes.
A new study reveals that B cells restrict the transendothelial migration of T cells in physiological inflammation in response to adiponectin, but that this mechanism is compromised in autoimmunity and is hence a novel avenue for therapy development.
Developing therapeutics for cancers targeting driver mutations in epigenetic regulators is a challenging frontier in cancer therapy. A new study identifies a pathway that, when activated, inhibits the actions of the histone methyltransferase DOT1L in MLL fusion leukemia.
A study involving a mouse model of Down syndrome and analysis of human postmortem brain samples indicates that hippocampal GABAA receptor signaling in Down syndrome may be excitatory. This advance promises new clinical applications in Down syndrome.
Type 2 diabetes occurs when the pancreatic beta cells fail to meet the increased insulin requirement in insulin-resistant individuals. A new therapeutic approach targeting glutamate receptors on beta cells improves insulin secretion and preserves beta cell mass.
Malaria is thought to have shaped the worldwide distribution of human ABO blood but the underlying molecular details of this process have only recently started to be revealed. A new study provides insights on how malaria parasites interact with ABO blood group sugars, mediating rosetting events that cause severe disease.
Experimental modeling of cancer typically uses in vitro culture of transformed cell lines or in vivo animal models. A new study using CRISPR-Cas9 to engineer oncogenic mutations into three-dimensional human colon organoid cultures yields insights into colorectal cancer tumorigenesis.
Osteoclasts are required for bone resorption. A new study in mice indicates that osteoclast differentiation is stabilized by DNA methylation at Irf8 (encoding interferon regulatory factor 8) mediated by DNA methyltransferase 3a (Dnmt3a), which suppresses Irf8 gene expression. The activity of Dnmt3 in osteoclasts requires elevated oxidative metabolism.
The NLRP3 inflammasome is involved in the molecular etiology of multiple autoinflammatory diseases. Two studies identify inhibitors of NLRP3 activation and might pave the way for new treatment options for a variety of diseases.
Pathogenic mutations of the genes encoding isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) occur in people with acute myeloid leukemia or other tumors. A new study identifies a dependence of IDH-mutated cells on the anti-apoptosis regulator BCL-2 and indicates a 'synthetic lethal' strategy for the treatment of leukemias.
A study of SIV-infected rhesus macaques suggests that T follicular helper (TFH) cells, a specialized CD4+ T cell subset within the B cell follicles, are a sanctuary for SIV that is largely inaccessible to CD8+ T cells. These findings may open new avenues for research aimed at eradicating HIV.
Obesity is a major risk factor for chronic disease. A new study in mice reveals that lowering levels of the signaling molecule serotonin outside of the brain reduces obesity and its complications by increasing brown adipose tissue (BAT) energy expenditure.
CD4+ helper T cells are immune cells that can specifically target cancer cells, but the antigens they recognize on tumor cells are mostly unknown. A new study shows that CD4+ T cells recognize peptides encoded by mutated genes in human melanoma, opening the way for new approaches to cancer immunotherapy.
