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Aims: Tumor-associated macrophages (TAM) is related to Ovarian cancer (OC) pathogenesis, but the exact mechanism remains unclear. This study investigated the expression of Kelch Domain Containing 8 A (KLHDC8A) in OC and the mechanism associated with TAM.
Main Methods: Bioinformatics analysis of differential expression genes between normal and OC tissues were analyzed based on the Tumor Genome Atlas (TCGA) databases. KLHDC8A mRNA expression was knocked down in normal epithelial cells (IOSE80), and then the effects of siKLHDC8A on the proliferation, invasion, migration and C5a secretion of IOSE80 cells were explored. THP1-derived macrophages were cultured with medium of NC-IOSE80 cells, siKLHDC8A-IOSE80 cells with or without C5aR antagonists.
Key Findings: KLHDC8A was lowly expressed in OC and negatively correlated with the infiltration of tumor-promoting macrophages, contributing to the survival of OC patients. Furthermore, siKLHDC8A promotes the proliferation, invasion and migration of IOSE80 cells and leads to polarization of pro-tumoral macrophages, which can be rescued by C5aR antagonists.
Significance: Our results indicated that KLHDC8A knockdown could modulate the development of OC by affecting macrophage polarization to pro-tumoral type via the C5a/C5aR/p65 NFκB signaling pathway. It may play an essential role as the tumor suppressor genes in diagnosis and treatment of OC.
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http://dx.doi.org/10.1016/j.cellimm.2024.104913 | DOI Listing |
Int J Nanomedicine
July 2025
Department of Respiratory Medicine, Shenyang 10th People's Hospital, Shenyang Chest Hospital, Shenyang, 110044, People's Republic of China.
Extracellular vesicles (EVs), serving as pivotal mediators of intercellular communication within the tumor microenvironment (TME), exert substantial regulatory influence on lung cancer progression and treatment resistance through their cargo of non-coding RNA (ncRNA). This comprehensive review systematically delineates the biogenesis mechanisms of EVs-ncRNA and their dualistic biological functions in lung carcinogenesis. Pro-tumoral ncRNA are selectively packaged into EVs through specialized sorting mechanisms, subsequently activating oncogenic pathways to potentiate tumor proliferation, invasion, and angiogenesis.
View Article and Find Full Text PDFJ Adv Res
June 2025
School of Chemical Science and Engineering, Department of Clinical Laboratory, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200092, PR China. Electronic address:
Introduction: Ion interference therapy has emerged as a promising new treatment for Osteosarcoma (OS). However, its efficacy is significantly restricted by inadequate hydrogen peroxide (HO) under the complex tumor microenvironment (TME).
Objectives: This study aimed to supply sufficient HO to enhance tumor therapy efficacy and address the limitations associated with ion interference.
Acta Pharm Sin B
April 2025
State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianj
Among tumor microenvironment (TME), the entire metabolic characteristics of tumor-resident cells are reprogrammed to benefit the expansion of tumor cells, which count on glutamine in large part to fuel the tricarboxylic acid cycle for energy generation and anabolic metabolism support. Endothelial cells that are abducted by tumor cells to form a pathological tumor vascular network for constructing the hypoxic immunosuppressive TME, also rely on glutaminolysis as the "engine" of angiogenesis. Additionally, the glutamine metabolic preference benefits the polarization of TAMs towards pro-tumoral M2 phenotype as well.
View Article and Find Full Text PDFAnn Med Surg (Lond)
June 2025
Department of Biomedical and Laboratory Science, Africa University, Mutare, Zimbabwe.
Neutrophils, essential components of the innate immune system, exhibit remarkable plasticity in the tumor microenvironment, shifting between anti-tumoral (N1) and pro-tumoral (N2) phenotypes. This functional dichotomy is particularly significant in breast cancer, where N1 neutrophils contribute to tumor suppression by enhancing cytotoxicity and immune activation, while N2 neutrophils promote tumor progression through immunosuppression, angiogenesis, and metastasis. The tumor microenvironment, driven by factors such as TGF-β, IL-6, and hypoxia, orchestrates this polarization, profoundly influencing disease progression and therapeutic outcomes.
View Article and Find Full Text PDFJ Nanobiotechnology
June 2025
Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
Background: Tumor-associated macrophages (TAMs) contribute significantly to immunosuppression in colorectal cancer liver metastasis (CRLM), leading to high aggressiveness and poor prognosis. However, the key molecules involved in shaping TAMs toward the pro-tumoral phenotype in CRLM remain unclear, limiting the development of macrophage-mediated immunotherapies for CRLM.
Results: In this study, we showed that DICER1 was highly expressed in TAMs and closely associated with M2 polarization in CRLM.