Publications by authors named "Michelle L Saetersmoen"
Background: Current prognostic variables can only partly explain the large outcome heterogeneity in diffuse large B cell lymphoma (DLBCL). We aimed to investigate the utility of systems-level protein and immune repertoire profiling for outcome prognostication in DLBCL.
Methods: In this retrospective study, we used proximity extension assay technology to quantify 81 immune-related proteins in serum or plasma in 2 independent cohorts in a total 111 DLBCL patients.
Article Synopsis
- Inhibitory signaling in natural killer (NK) cells enhances their response to activation, but the specific mechanisms behind this process are still not fully understood.
- The study reveals that educated NK cells with specific inhibitory receptors gather granzyme B in secretory lysosomes near the centrosome, a process that operates independently of general transcription factors that control cell functions.
- Additionally, interference with certain intracellular calcium signals affects NK cell activity, while inhibiting specific lysosomal pathways can boost granzyme B levels and mimic the heightened functionality seen in educated NK cells.
Article Synopsis
- The study explores the potential of using allogeneic NK cells as a cancer immunotherapy and highlights the current methods of expanding these cells in lab settings, which often involve high levels of IL-15 stimulation.
- It identifies a problem where NK cells become overly dependent on IL-15, leading to significant stress and cell death when IL-15 is suddenly removed after expansion.
- The research links NK cell survival to the balance of BCL-2 and BIM proteins, and shows that withdrawal from IL-15 induces a specific harmful form of BIM, providing insights for improving NK cell therapies in cancer treatment.
Cell therapy is emerging as a very promising therapeutic modality against cancer, spearheaded by the clinical success of chimeric antigen receptor (CAR) modified T cells for B cell malignancies. Currently, FDA-approved CAR-T cell products are based on engineering of autologous T cells harvested from the patient, typically using a central manufacturing facility for gene editing before the product can be delivered to the clinic and infused to the patients. For a broader implementation of advanced cell therapy and to reduce costs, it would be advantageous to use allogeneic "universal" cell therapy products that can be stored in cell banks and provided upon request, in a manner analogous to biopharmaceutical drug products.
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