98%
921
2 minutes
20
Background: The heterogeneity of prognosis and treatment benefits among patients with gliomas is due to tumor microenvironment characteristics. However, biomarkers that reflect microenvironmental characteristics and predict the prognosis of gliomas are limited. Therefore, we aimed to develop a model that can effectively predict prognosis, differentiate microenvironment signatures, and optimize drug selection for patients with glioma.
Materials And Methods: The CIBERSORT algorithm, bulk sequencing analysis, and single-cell RNA (scRNA) analysis were employed to identify significant cross-talk genes between M2 macrophages and cancer cells in glioma tissues. A predictive model was constructed based on cross-talk gene expression, and its effect on prognosis, recurrence prediction, and microenvironment characteristics was validated in multiple cohorts. The effect of the predictive model on drug selection was evaluated using the OncoPredict algorithm and relevant cellular biology experiments.
Results: A high abundance of M2 macrophages in glioma tissues indicates poor prognosis, and cross-talk between macrophages and cancer cells plays a crucial role in shaping the tumor microenvironment. Eight genes involved in the cross-talk between macrophages and cancer cells were identified. Among them, periostin (), chitinase 3 like 1 (), serum amyloid A1 (), and matrix metallopeptidase 9 () were selected to construct a predictive model. The developed model demonstrated significant efficacy in distinguishing patient prognosis, recurrent cases, and characteristics of high inflammation, hypoxia, and immunosuppression. Furthermore, this model can serve as a valuable tool for guiding the use of trametinib.
Conclusions: In summary, this study provides a comprehensive understanding of the interplay between M2 macrophages and cancer cells in glioma; utilizes a cross-talk gene signature to develop a predictive model that can predict the differentiation of patient prognosis, recurrence instances, and microenvironment characteristics; and aids in optimizing the application of trametinib in glioma patients.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576925 | PMC |
http://dx.doi.org/10.32604/or.2024.046191 | DOI Listing |
J Biomed Sci
September 2025
Division of Gastroenterology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Oncometabolites are aberrant metabolic byproducts that arise from mutations in enzymes of the tricarboxylic acid (TCA) cycle or related metabolic pathways and play central roles in tumor progression and immune evasion. Among these, 2-hydroxyglutarate (2-HG), succinate, and fumarate are the most well-characterized, acting as competitive inhibitors of α-ketoglutarate-dependent dioxygenases to alter DNA and histone methylation, cellular differentiation, and hypoxia signaling. More recently, itaconate, an immunometabolite predominantly produced by activated macrophages, has been recognized for its dual roles in modulating inflammation and tumor immunity.
View Article and Find Full Text PDFNat Aging
September 2025
Department of Neurology, Mental and Neurological Disease Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Aging is a major risk factor for various neurological disorders, including Alzheimer's disease, and is associated with the accumulation of senescent cells, which can themselves propagate the senescence process through paracrine signaling. Migrasomes are organelles that form during cellular migration, detach from parent cells and mediate intercellular communication. Here we demonstrate that border-associated macrophages (BAMs) acquire senescence-associated properties during early brain aging, possibly due to prolonged exposure to amyloid beta.
View Article and Find Full Text PDFNature
September 2025
Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Monocyte-derived macrophages (mo-macs) often drive immunosuppression in the tumour microenvironment (TME) and tumour-enhanced myelopoiesis in the bone marrow fuels these populations. Here we performed paired transcriptome and chromatin accessibility analysis over the continuum of myeloid progenitors, circulating monocytes and tumour-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. We show that lung tumours prime accessibility for Nfe2l2 (NRF2) in bone marrow myeloid progenitors as a cytoprotective response to oxidative stress, enhancing myelopoiesis while dampening interferon response and promoting immunosuppression.
View Article and Find Full Text PDFOncogene
September 2025
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Pancreatic cancer is a highly aggressive malignancy with a dismal prognosis, characterized by a complex tumor microenvironment that promotes immunosuppression and limits the efficacy of immune checkpoint blockade (ICB) therapy. Fibroblast activation protein (FAP) is overexpressed in the tumor stroma and represents a promising target for therapeutic intervention. Here, we developed a novel antibody-drug conjugate (ADC) targeting FAP, and investigated its anti-tumor activity and ability to enhance ICB efficacy in pancreatic cancer.
View Article and Find Full Text PDFBiochim Biophys Acta Rev Cancer
September 2025
Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China; Fujian Abdominal Surgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350001, China; National Regional Medical Cente
Pancreatic ductal adenocarcinoma (PDAC) exhibits persistent resistance to immunotherapy, with a 5-year survival rate around 10 %. The CD39-CD73-adenosine axis emerges as a critical mediator of immune evasion in PDAC, generating pathologically elevated adenosine concentrations that systematically suppress anti-tumor immunity. This purinergic pathway operates through sequential ATP hydrolysis by CD39 and CD73 ectonucleotidases, producing adenosine that engages four G-protein-coupled receptors (A1, A2A, A2B, A3) to orchestrate comprehensive immunosuppression.
View Article and Find Full Text PDF