ArticleAging2024
Activation of Notch-1 signaling pathway in macrophages to secrete PD-L1 and regulate cytotoxicity of CAR-T cells in diffuse large B-cell lymphoma.
Article in Aging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Overcoming CAR-T bottlenecks in high-risk DLBCL: a molecular subtyping enhancement strategy.Cancer cell international · 2025Review
- ATF6 activation promotes tumorigenesis and drug resistance in diffuse large B-cell lymphoma (DLBCL) by regulating the mTOR/S6K signaling pathway.Discover oncology · 2025Article
- Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review.International journal of molecular sciences · 2024Review
- Endoplasmic reticulum stress-a key guardian in cancer.Cell death discovery · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo investigate the mechanism of action of the Notch-1/IRE1/XBP1s signaling pathway in diffuse large B-cell lymphoma (DLBCL).
methodsThe expressions of relevant proteins were detected by Western blotting. The effect of myeloid-specific knockout of Notch-1 on lymphoma progression was observed by mouse tumor transplantation and imaging. The apoptosis of chimeric antigen receptor T-cell therapy (CAR-T) cells were detected by flow cytometry, and the proliferation of CAR-T cells was detected by wound healing assay and cell counting kit-8 (CCK8) assay.
resultsLymphoma cells mediated the Notch-1 signaling pathway in bone marrow-derived macrophages and promoted the activation of STAT3 and STAT6 in bone marrow-derived macrophages. Myeloid-specific knockout of Notch-1 could inhibit the progression of lymphoma. Lymphoma cells enhanced the expression of p-PERK, p-IRE1α, ATF6, IL-6, IL-4, p-AKT, CD9, CD63 and PD-L1 in bone marrow-derived macrophages by mediating the Notch-1 signaling pathway. Knockout of Notch-1 in macrophages alleviated, to some extent, the suppression of killing activity of CAR-T cells, while activation of Notch-1 in macrophages inhibited proliferation and promoted apoptosis of CAR-T cells. The PD-L1 antibody significantly restored the cytotoxicity and proliferation of CAR-T cells, and inhibited their apoptosis.
conclusionActivation of the Notch-1/IRE1/XBP1s signaling pathway in myeloid macrophages promotes the secretion of IL-6 and IL-4 as well as PD-L1, thereby inhibiting the activity and proliferation of CAR-T cells and promoting their apoptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.