Transgenic coexpression of a class I–restricted tumor antigen–specific T cell receptor (TCR) and CD8αβ (TCR8) redirects antigen specificity of CD4+ T cells. Reinforcement of biophysical properties and early TCR signaling explain how redirected CD4+ T cells recognize target cells, but the transcriptional basis for their acquired antitumor function remains elusive. We, therefore, interrogated redirected human CD4+ and CD8+ T cells by single-cell RNA sequencing and characterized them experimentally in bulk and single-cell assays and a mouse xenograft model. TCR8 expression enhanced CD8+ T cell function and preserved less differentiated CD4+ and CD8+ T cells after tumor challenge. TCR8+CD4+ T cells were most potent by activating multiple transcriptional programs associated with enhanced antitumor function. We found sustained activation of cytotoxicity, costimulation, oxidative phosphorylation– and proliferation-related genes, and simultaneously reduced differentiation and exhaustion. Our study identifies molecular features of TCR8 expression that can guide the development of enhanced immunotherapies.
The microalgae Tetradesmus obliquus is able to maintain a high photosynthetic efficiency under nitrogen limitation and is considered a promising green microalgae for sustainable production of diverse compounds, including biofuels. Here, we report the first draft whole-genome shotgun sequencing of T. obliquus. The final assembly comprises 108,715,903 bp with over 1,368 scaffolds.
Microplastics (MPs) have gained a high degree of public interest since they are associated with the global release of plastics into the environment. Various studies have confirmed the presence of MPs throughout the food chain. However, information on the ingestion of MPs via the consumption of many commonly consumed foods like dairy products are scarce due to the lack of studies investigating the “contamination” of this food group by MPs. This lack of occurrence data is mainly due to the absence of robust analytical methods capable of reliably quantifying MPs with size < 20 µm in foods. In this work, a new methodology was developed to accurately determine and characterize MPs in milk-based products using micro-Raman (μRaman) technology, entailing combined enzymatic and chemical digestion steps. This is the first time that the presence of relatively low amounts of small-sized MP (≥ 5 µm) have been reported in raw milk collected at farm just after the milking machine and in some processed commercial liquid and powdered cow’s milk products.
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