Senescent cells, which accumulate with age, exhibit a pro-inflammatory senescence-associated secretory phenotype (SASP) that includes the secretion of cytokines, lipids, and extracellular vesicles (EVs). Here, we established an in vitro model of senescence induced by Raf-1 oncogene in RAW 264.7 murine macrophages (MΦ) and compared them to senescent MΦ found in mouse lung tumors or primary macrophages treated with hydrogen peroxide.
View Article and Find Full Text PDFHarnessing the immunogenic potential of senescent cells may be a viable but context-dependent opportunity to boost antitumor immunity.
View Article and Find Full Text PDFSenescent cells play relevant but context-dependent roles during tumorigenesis. Here, in an oncogenic Kras-driven lung cancer mouse model, we found that senescent cells, specifically alveolar macrophages, accumulate early in neoplasia. These macrophages have upregulated expression of p16 and Cxcr1, are distinct from previously defined subsets and are sensitive to senolytic interventions, and suppress cytotoxic T cell responses.
View Article and Find Full Text PDFCellular senescence is the dynamic process of durable cell-cycle arrest. Senescent cells remain metabolically active and often acquire a distinctive bioactive secretory phenotype. Much of our molecular understanding in senescent cell biology comes from studies using mammalian cell lines exposed to stress or extended culture periods.
View Article and Find Full Text PDFIn response to a variety of cancer-inducing stresses, cells may engage a stable cell cycle arrest mechanism, termed cellular senescence, to suppress the proliferation of preneoplastic cells. Despite this cell intrinsic tumor suppression, senescent cells have also been implicated as active contributors to tumorigenesis by extrinsically promoting many hallmarks of cancer, including evasion of the immune system. Here, we discuss these dual, and seemingly contradictory, roles of senescence during tumorigenesis.
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