12 research outputs found

    Consequential considerations when mapping tRNA fragments

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    We examine several of the choices that went into the design of tDRmapper, a recently reported tool for identifying transfer RNA (tRNA) fragments in deep sequencing data, evaluate them in the context of currently available knowledge, and discuss their potential impact on the output that the tool generates

    A Fleeting Glimpse Inside microRNA, Epigenetics, and Micropeptidomics

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    MicroRNAs (miRs) are important regulators of gene expression in numerous biological processes. Their maturation process is herein described, including the most updated insights from the current literature. Circa 2000 miR sequences have been identified in the human genome, with over 50,000 miR-target interactions, including enzymes involved in epigenetic modulation of gene expression. Moreover, some "pieces of RNA" previously annotated as noncoding have been recently found to encode micropeptides that carry out critical mechanistic functions in the cell. Advanced techniques now available will certainly allow a precise scanning of the genome looking for micropeptides hidden within the "noncoding" RNA

    B cells and tertiary lymphoid structures promote immunotherapy response

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    International audienceTreatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers1-10 and strategies to augment clinical response have largely focused on the T cell compartment. However, other immune subsets may also contribute to anti-tumour immunity11-15, although these have been less well-studied in ICB treatment16. A previously conducted neoadjuvant ICB trial in patients with melanoma showed via targeted expression profiling17 that B cell signatures were enriched in the tumours of patients who respond to treatment versus non-responding patients. To build on this, here we performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumours of responders versus non-responders. Our findings were corroborated using a computational method (MCP-counter18) to estimate the immune and stromal composition in this and two other ICB-treated cohorts (patients with melanoma and renal cell carcinoma). Histological evaluation highlighted the localization of B cells within tertiary lymphoid structures. We assessed the potential functional contributions of B cells via bulk and single-cell RNA sequencing, which demonstrate clonal expansion and unique functional states of B cells in responders. Mass cytometry showed that switched memory B cells were enriched in the tumours of responders. Together, these data provide insights into the potential role of B cells and tertiary lymphoid structures in the response to ICB treatment, with implications for the development of biomarkers and therapeutic targets
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