Cellular and secretome profiling uncover immunological biomarkers in the prognosis of renal cell carcinoma patientsTong, Kremer, Neo
et alOncoimmunology (2025) 14 (1), 2481109
Abstract: Renal cell carcinoma (RCC) is recognized as an immunogenic tumor, yet tumor-infiltrating lymphocytes often exhibit diminished effector function. However, the mechanisms underlying reduced T and NK cell activity in RCC remain unclear. Here, we examined the immune contexture in RCC patients undergoing nephrectomy to identify immune-related biomarkers associated with disease progression. Immune cell phenotypes and secretion profiles were assessed using flow cytometry and Luminex multiplex analysis. Supervised multivariate analysis revealed several changes of which frequencies of T and NK cells expressing CCR5, CXCR3, and PD-1 were elevated within tumors compared with peripheral blood. In addition, higher levels of regulatory T cells, PD-1+, and CXCR3+ T and NK cells were observed in patients with relapse following nephrectomy. With regards to soluble factors, tumor-derived CXCL8 was associated with higher Fuhrman grade and increased frequency of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). These biomarkers demonstrate potential relevance in the progression of RCC and merit further investigation in prospective studies.
Alveolar epithelial type 2 cell specific loss of IGFBP2 activates inflammation in COVID-19Pujadas, Chin, Sankpal
et alRespir Res (2025) 26 (1), 111
Abstract: The coronavirus disease 2019 (COVID-19) global pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, our understanding of SARS-CoV-2-induced inflammation in alveolar epithelial cells remains very limited. The contributions of intracellular insulin-like growth factor binding protein-2 (IGFBP2) to SARS-CoV-2 pathogenesis are also unclear. In this study, we have uncovered a critical role for IGFBP2, specifically in alveolar epithelial type 2 cells (AEC2), in the immunopathogenesis of COVID-19. Using bulk RNA sequencing, we show that IGFBP2 mRNA expression is significantly downregulated in primary AEC2 cells isolated from fibrotic lung regions from patients with COVID-19-acute respiratory distress syndrome (ARDS) compared to those with idiopathic pulmonary fibrosis (IPF) alone or IPF with a history of COVID-19. Using multicolor immunohistochemistry, we demonstrated that IGFBP2 and its selective ligands IGF1 and IGF2 were significantly reduced in AEC2 cells from patients with COVID-ARDS, IPF alone, or IPF with COVID history than in those from age-matched donor controls. Further, we demonstrated that lentiviral expression of Igfbp2 significantly reduced mRNA expression of proinflammatory cytokines-Tnf-α, Il1β, Il6, Stat3, Stat6 and chemokine receptors-Ccr2 and Ccr5-in mouse lung epithelial cells challenged with SARS-CoV-2 spike protein injury (S2; 500 ng/mL). Finally, we demonstrated higher levels of cytokines-TNF-α; IL-6 and chemokine receptor-CCR5 in AEC2 cells from COVID-ARDS patients compared to the IPF alone and the IPF with COVID history patients. Altogether, these data suggest that anti-inflammatory properties of IGFBP2 in AEC2 cells and its localized delivery may serve as potential therapeutic strategy for patients with COVID-19.© 2025. The Author(s).
Electroacupuncture at 5/100 Hz alleviates neuropathic pain in rats by inhibiting the CCL3/CCR5 axis in the spinal cordWang, Ye, Yin
et alAcupunct Med (2025)
Abstract: Typically, neuropathic pain (NP) is difficult to manage as it is refractory to conventional medications. Electroacupuncture (EA) at 5/100 Hz has emerged as an effective and promising treatment for NP; however, its mechanism of action is still uncertain. Accordingly, this study investigated the alleviatory mechanism of EA in chronic compression injury (CCI)-induced chronic pain via the C-C chemokine ligand 3 / C-C chemokine receptor type 5 (CCL3/CCR5) axis.The CCI model was established in rats to induce NP. Mechanical and thermal hyperalgesia were assessed with von Frey and Hargreaves tests, respectively. From day 8 after CCI, EA (5/100 Hz) was performed for 1 week (30 min/day). CCL3 and CCR5 expression was detected with Western blotting and immunofluorescence. Glial cell activation was determined through co-labeling of neurons and glial cells with antibodies against CCL3 and CCR5. The release of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was tested with enzyme-linked immunosorbent assay (ELISA).EA markedly ameliorated CCI-induced chronic NP in rats and reduced CCL3 and CCR5 expression in the rat spinal cord. CCL3 and CCR5 were co-expressed by neurons and microglia in the central nervous system. In addition, EA also repressed the activation of glial cells and levels of IL-1β, IL-6 and TNF-α.EA may mitigate chronic NP in rats by blocking the CCL3/CCR5 axis in the spinal cord. In addition, EA appeared to exert anti-inflammatory and analgesic effects by suppressing glial cell activation. These findings add to our understanding of the mechanism of EA-induced analgesia.
Androgen receptor-induced lncRNA SOX2-OT promotes triple-negative breast cancer tumorigenesis via targeting miR-320a-5p/CCR5 axisHu, Bian, Chen
et alJ Biol Chem (2025)
Abstract: Our previous study showed that androgen receptor (AR) promotes triple-negative breast cancer (TNBC) cells tumorigenesis, but the underlying mechanisms remain unclear. Herein, using microarray analysis of lncRNA expression profiles, we identified an AR-related lncRNA SOX2-OT in TNBC. We found that AR could promote TNBC tumorigenesis by acting as a transcription factor to activate the expression of SOX2-OT. Mechanistic analysis demonstrated that SOX2-OT serves as a molecular sponge for miR-320a-5p to regulate the expression of CCR5. In addition, SOX2-OT promotes TNBC cell proliferation and inhibits apoptosis in a miR-320a-5p-dependent manner. Using a xenograft mouse model, we found SOX2-OT/CCR5 axis could promote TNBC tumorigenesis in vivo. Importantly, the AR/SOX2-OT/miR-320a-5p/CCR5 axis is manifested in the tissues of 165 TNBC patients. Collectively, our results suggest that SOX2-OT can regulate AR-induced TNBC tumorigenesis through the miR-320a-5p/CCR5 signaling axis, and reveal the great potential of targeting SOX2-OT for the treatment of TNBC patients.Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
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