Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells Graphical abstract Highlights d Integrated, single-cell RNA-and BCR-seq in three organs after influenza infection d Switched, mutated memory B cells are continuously produced from germinal centers d Lung memory B cells originate from lymphoid organs and assume residency phenotype d Memory B cells are derived from both low-and high-affinity GC precursors
Highlights d scRNA-seq reveals early divergence of PBs, GCBCs, and MBCs from the common precursor d Unlike PBs and GCBCs, eMBCs remain transcriptionally similar to the precursors d Cell cycle exit of eMBCs is driven by the decline in antigen availability d Provision of antigen excess drives generation of a new PB wave from eMBCs
Exosomes are small extracellular membrane vesicles important in intercellular communication, with their oncogenic cargo attributed to tumor progression and pre‐metastatic niche formation. To gain an insight into key differences in oncogenic composition of exosomes, human non‐malignant epithelial and pancreatic cancer cell models and purified and characterized resultant exosome populations are utilized. Proteomic analysis reveals the selective enrichment of known exosome markers and signaling proteins in comparison to parental cells. Importantly, valuable insights into oncogenic exosomes (362 unique proteins in comparison to non‐malignant exosomes) of key metastatic regulatory factors and signaling molecules fundamental to pancreatic cancer progression (KRAS, CD44, EGFR) are provided. It is reported that oncogenic exosomes contain factors known to regulate the pre‐metastatic niche (S100A4, F3, ITGβ5, ANXA1), clinically‐relevant proteins which correlate with poor prognosis (CLDN1, MUC1) as well as protein networks involved in various cancer hallmarks including proliferation (CLU, CAV1), invasion (PODXL, ITGA3), metastasis (LAMP1, ST14) and immune surveillance escape (B2M). The presence of these factors in oncogenic exosomes offers an understanding of select differences in exosome composition during tumorigenesis, potential components as prognostic and diagnostic biomarkers in pancreatic cancer, and highlights the role of exosomes in mediating crosstalk between tumor and stromal cells.
Despite the rapid development in the field of oncology, cancer remains the second cause of mortality worldwide, with the number of new cases expected to more than double in the coming years. Chemotherapy is widely used to decelerate or stop tumour development in combination with surgery or radiation therapy when appropriate, and in many cases this improves the symptomatology of the disease. Unfortunately though, chemotherapy is not applicable to all patients and even when it is, there are many cases where a successful initial treatment period is followed by chemotherapeutic drug resistance. This is caused by a number of reasons, ranging from the genetic background of the patient (innate resistance) to the formation of tumour-initiating cells (acquired resistance). In this review, we discuss the potential role of PDK1 in the development of chemoresistance in different types of malignancy, and the design and application of potent inhibitors which can promote chemosensitization.
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