Project description:Although T cell activation is closely linked to internalization of the T cell antigen receptor (TCR), relatively few studies have examined the release of TCRs via shedding of T cell microvilli following physical interaction with cognate antigen-presenting cells. In this study, we investigated the physiological implications of the release of TCRs and other external membrane components. We term this event “trogocytic molting”, as it occurs through a combined process of trogocytosis and enzymatic vesiculation of microvillar membrane structures. Surprisingly, in contrast to TCR internalization, this event leads to rapid upregulation of surface TCRs and remarkable metabolic reprogramming of cholesterol and fatty acids synthesis to meet the demands of clonal expansion, which drives multiple rounds of division and cell survival. These findings suggest that, contrary to the long-standing paradigm that emphasizes the importance of TCR internalization, external membrane loss, including TCRs, is a significant mechanism for clonal expansion
Project description:B10.PL mice with severe (stage 2.5-3) experimental autoimmune encephalomyelitis were treated with placebo or 200 ng 1,25(OH)2D3. Six hours later, the spinal cords were harvested and mRNA was extracted for microarray analysis. Naive mice serve as controls. Individual samples were hybridized to individual microarrays. Keywords = Experimental autoimmune encephalomyelitis Keywords = multiple sclerosis Keywords = 1 Keywords = 25(OH)2D3 Keywords: repeat sample
Project description:In this comprehensive study, the authors have developed concise models integrating clinical, genomic and transcriptomic features to predict intrinsic resistance to anti-PD1 Immune Checkpoint Blockade (ICB) treatment in individual tumors. It's important to note that their validation was performed in smaller, independent cohorts, constrained by data availability. The authors have developed two Logistic Regression based models for Ipilimumab treated and Ipilimumab naive patients with metastatic melanoma. The main predictive features for the Ipilimumab treated patients are MHC-II HLA, LDH at treatment initiation and the presence of lymph node metastases (LN met), chosen using forward selection methodology. The main predictive features for the Ipilimumab naive patients are tumor heterogeneity, tumor ploidy and tumor purity, chosen using forward selection methodology.
Please note that in these models, the output ‘1’ means progressive disease (PD) and ‘0’ means non-PD. The original GitHub repository can be accessed at https://github.com/vanallenlab/schadendorf-pd1
