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Secreted phosphosprotein 1 (SPP1) tumor-associated macrophages (TAM) are abundant tumor myeloid cells that are immunosuppressive, pro-tumorigenic, and have a highly negative prognostic factor. Despite this, there is a lack of efficient TAM-specific therapeutics capable of reducing SPP1 expression. Here, on a phenotypic screen is reported to identify small molecule SPP1 modulators in macrophages. Several hits and incorporated them into a TAM-avid systemic nanoformulation are identified. It is shown that the lead compound (CANDI460) can down-regulate SPP1 in vitro and in vivo and lead to tumor remissions in different murine models. These findings are important as they offer a promising avenue for developing novel therapeutic strategies targeting TAM.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775521 | PMC |
http://dx.doi.org/10.1002/advs.202410360 | DOI Listing |
Zhong Nan Da Xue Xue Bao Yi Xue Ban
May 2025
Department of Pathology, First Clinical College, Changzhi Medical College, Changzhi 046000.
Objectives: Acute lung injury (ALI) is an acute respiratory failure syndrome characterized by impaired gas exchange. Due to the lack of effective targeted drugs, it is associated with high mortality and poor prognosis. (TW) has demonstrated anti-inflammatory activity in the treatment of various diseases.
View Article and Find Full Text PDFNan Fang Yi Ke Da Xue Xue Bao
August 2025
School of Mathematics and Statistics, Guangdong University of Technology, Guangzhou 510520, China.
Objectives: To explore the key role of myeloid-derived suppressive cells (MDSCs) in pre-metastatic niche (PMN) and analyze their interrelationships with the main components in the microenvironment using a mathematical model.
Methods: Mathematical descriptions were used to systematically analyze the functions of MDSCs in tumor metastasis and elucidate their association with the major components (vascular endothelial cells, mesenchymal stromal cells, and cancer-associated macrophages) contributing to the formation of the pre-metastatic microenvironment. Based on the formation principle of the pre-metastatic microenvironment of tumors, the key biological processes were assumed to construct a coupled partial differential diffusion equation model.
Nan Fang Yi Ke Da Xue Xue Bao
August 2025
Department of Biochemistry and Molecular Biology, Bengbu Medical University, Bengbu 233030, China.
Objectives: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer.
Methods: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry.
Nan Fang Yi Ke Da Xue Xue Bao
August 2025
Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical University, Bengbu 233030, China.
Objectives: To investigate the effect of avitinib for suppressing NLRP3 inflammasome activation and alleviating septic shock and explore the underlying mechanism.
Methods: Mouse bone marrow-derived macrophages (BMDM), human monocytic leukemia cell line THP-1, and peripheral blood mononuclear cells (PBMC) isolated from healthy volunteers were pre-treated with avitinib, followed by activation of the canonical NLRP3 inflammasome using agonists including nigericin, monosodium urate (MSU) crystals, or adenosine triphosphate (ATP). Non-canonical NLRP3 inflammasome activation was induced intracellular transfection of lipopolysaccharide (LPS).
Nan Fang Yi Ke Da Xue Xue Bao
August 2025
Department of Urology, Third Affiliated Hospital of Southern Medical University, Guangzhou 510000, China.
Objectives: To identify immunosuppressive neutrophil subsets in patients with prostate cancer (PCa) and construct a risk prediction model for prognosis and immunotherapy response of the patients based on these neutrophil subsets.
Methods: Single-cell and transcriptome data from PCa patients were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Neutrophil subsets in PCa were identified through unsupervised clustering, and their biological functions and effects on immune regulation were analyzed by functional enrichment, cell interaction, and pseudo-time series analyses.