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Phagocytic clearance of apoptotic cancer cells (efferocytosis) by tumor-associated macrophages (TAMs) contributes in a substantial manner to the establishment of an immunosuppressive tumor microenvironment. This puts in context our observation that the female steroid hormone 17β-estradiol (E2) facilitates tumor immune resistance through cancer cell extrinsic Estrogen Receptor (ERalpha;) signaling in TAMs. Notable was the finding that E2 induces the expression of CX3CR1 in TAMs to enable efferocytosis of apoptotic cancer cells which results in the suppression of type I interferon (IFN) signaling.
View Article and Find Full Text PDFYAP regulates periosteal expansion in fracture repair.
bioRxiv
December 2024
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Bone fracture repair initiates by periosteal expansion. The periosteum is typically quiescent, but upon fracture, periosteal cells proliferate and contribute to bone fracture repair. The expansion of the periosteum is regulated by gene transcription; however, the molecular mechanisms behind periosteal expansion are unclear.
View Article and Find Full Text PDFMolecular and spatial analysis of ganglion cells on retinal flatmounts: diversity, topography, and perivascularity.
bioRxiv
December 2024
Department of Ophthalmology, School of Medicine, University of California San Francisco, San Francisco, CA, USA.
Diverse retinal ganglion cells (RGCs) transmit distinct visual features from the eye to the brain. Recent studies have categorized RGCs into 45 types in mice based on transcriptomic profiles, showing strong alignment with morphological and electrophysiological properties. However, little is known about how these types are spatially arranged on the two-dimensional retinal surface-an organization that influences visual encoding-and how their local microenvironments impact development and neurodegenerative responses.
View Article and Find Full Text PDFImpaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signaling.
Immunity
December 2024
Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW 2052, Australia; Clinical Immunogenomics Research Consortium Australasia (CIRCA), Darlinghurst, NSW 2010, Australia. Electronic address:
Article Synopsis
- T follicular helper (Tfh) cells, which are important for antibody production, rely heavily on the immunoreceptor PD-1, and its deficiency leads to weakened Tfh functions and impaired immune responses in mice.
- Individuals lacking PD-1 or PD-L1 demonstrate fewer memory B cells and diminished antibody responses, highlighting the critical role of these molecules in immune system functionality.
- PD-1 influences both the intrinsic and extrinsic aspects of B cell memory and antibody production, suggesting that disruptions in PD-1 signaling can lead to complications in immune responses, especially during anti-PD-1-PD-L1 therapies.
From precursor to cancer: decoding the intrinsic and extrinsic pathways of pancreatic intraepithelial neoplasia progression.
Carcinogenesis
November 2024
Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD 21231, United States.
This review explores the progression of pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma through a dual lens of intrinsic molecular alterations and extrinsic microenvironmental influences. PanIN development begins with Kirsten rat sarcoma viral oncogene (KRAS) mutations driving PanIN initiation. Key additional mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein p53 (TP53), and mothers against decapentaplegic homolog 4 (SMAD4) disrupt cell cycle control and genomic stability, crucial for PanIN progression from low-grade to high-grade dysplasia.
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