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Two papers in this issue widen the spectrum of known mechanisms used by tumors to escape therapy. By sequencing cell-free plasma DNA from lung cancer patients treated with an epidermal growth factor receptor (EGFR) inhibitor, Thress et al. reveal a new EGFR-resistance mutation. Whole-exome sequencing of samples from patients with acute lymphoblastic leukemia led Li et al. to mutations in the phosphoribosyl pyrophosphate synthetase 1 gene (PRPS1) and a new chemotherapy-resistance mechanism. Cover image: stuartmiles99/iStock/ Thinkstock
Recent news of raids on research budgets illustrates how precarious government funding of scientific research has become. In an era of unprecedented momentum in the development of technologies and therapies for studying and treating disease, opportunities for new discoveries must not be lost due to shortsighted budgetary concerns.
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.
Cyclophilin A, secreted by bone marrow endothelial cells, acts as a chemotactic factor for myeloma cells, which helps explain their homing to the bone marrow and suggests a potential new therapeutic strategy.
Crystal Mackall and colleagues report that antigen-independent signaling of chimeric antigen receptors (CARs) causes T cell exhaustion and reduced therapeutic efficacy of CAR T cells that can be overcome by incorporating the 4-1BB costimulatory domain into the CAR.
A high percentage of smooth muscle cells in atherosclerotic lesions lose expression of smooth muscle marker proteins and acquire the phenotype of other cell types, a process of functional importance in lesion pathogenesis that is controlled by the transcription factor KLF4.