Neutrophils matter: New clinical insights on their role in the progression of metastatic breast cancer

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Abstract Background Metastatic breast cancer (BC) remains a significant clinical challenge, needing innovative strategies to improve disease management and extend patient survival. Increased neutrophil levels have been observed in both peripheral blood tumor tissues of patients with different types cancer, often being associated poor outcomes. These findings suggest crucial role for neutrophils progression, raising interest neutrophil-based therapies. However, the functional phenotypic heterogeneity complicates their therapeutic targeting. This study aims investigate impact immunosuppressive, protumor low-density (LDN) metastatic BC, comparing them normal high-density (HDN) better understand progression. Methods LDN HDN subpopulations were isolated from 151 BC (72 metastatic, 79 non-metastatic) using density gradient centrifugation. Their frequency, phenotype, function analyzed by flow cytometry vitro experiments. Correlations between data evaluated, alongside individual longitudinal assessments. Results accumulated significantly patients, particularly those disease. Elevated these faster progression reduced life expectancy, regardless site. Longitudinal analysis revealed that higher percentages correlated adverse events, whereas lower linked stable Functionally, exhibited properties, including elevated expressions PD-L1 MMP-9, contributing immunosuppression metastasis. Unlike HDN, which demonstrated cytotoxicity against cells, failed reduce cell line viability 3D co-cultures. Notably, lines exposed LDN-conditioned medium showed increased invasive capacity proliferation, while T cells cultured same displayed impaired activation, likely due effect arginase. Conclusion Our results highlighted secreted factors as major drivers aggressiveness. incorporating assessment into practice could aid identifying high-risk enable more personalized treatment approaches. Furthermore, our strengthen relevance targeting specific subsets or functions

Language: Английский

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Tumor-infiltrating myeloid cells; mechanisms, functional significance, and targeting in cancer therapy

Cellular Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Tumor-infiltrating myeloid cells (TIMs), which encompass tumor-associated macrophages (TAMs), neutrophils (TANs), myeloid-derived suppressor (MDSCs), and dendritic (TADCs), are of great importance in tumor microenvironment (TME) integral to both pro- anti-tumor immunity. Nevertheless, the phenotypic heterogeneity functional plasticity TIMs have posed challenges fully understanding their complexity roles within TME. Emerging evidence suggested that presence is frequently linked prevention cancer treatment improvement patient outcomes survival. Given pivotal function TME, recently been recognized as critical targets for therapeutic approaches aimed at augmenting immunostimulatory cell populations while depleting or modifying those immunosuppressive. This review will explore important properties related immunity, angiogenesis, metastasis. We also document latest strategies targeting preclinical clinical settings. Our objective illustrate potential immunological may improve existing treatments.

Language: Английский

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Integrated analysis reveals an immune evasion prognostic signature for predicting the overall survival in patients with hepatocellular carcinoma

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 18, 2025

The development of immunotherapy has enriched the treatment hepatocellular carcinoma (HCC), but efficacy is not as expected, which may be due to immune evasion. Immune evasion related microenvironment HCC, there little research on it. We employed unsupervised clustering analysis categorize patients from TCGA based 182 evasion-related genes (IEGs). utilized single-sample gene set enrichment (ssGSEA) and CIBERSORT calculate differences in cell infiltration between clusters. cells immune-related pathways were assessed using GSEA. constructed an escape prognosis signature (IEPS) univariate Cox LASSO algorithms evaluated predictive performance IEPS with receiver operating characteristic (ROC) curves survival curves. Additionally, we established a nomogram for clinical application IEPS. IHC validated expression Carbamoyl phosphate synthetase 2, Aspartate transcarbamylase, Dihydroorotase (CAD) Phosphatidylinositol Glycan Anchor Biosynthesis Class U (PIGU) HCC. transfected liver cancer lines siRNA overexpression plasmids, confirmed relationship CAD, PIGU, potential downstream TGF-β1 HCC qRT-PCR Western blot. Finally, tumor response CAD animal model. Unsupervised IEGs divided into two groups. There significant characteristics groups patients. Scoring revealed that higher scores associated poorer overall (OS). Validation was performed ICGC database. TIME indicated high-IEPS group immunosuppressive state, possibly increase Treg infiltration. Compared normal cells, expressed levels PIGU. Cellular experimental results showed positive correlation PIGU expression. Animal experiments demonstrated significantly promoted progression, strong prognostic value patients, provide perspectives new biomarkers therapeutic targets

Language: Английский

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The role of neutrophils in osteosarcoma: insights from laboratory to clinic

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 8, 2024

Osteosarcoma, a highly aggressive malignant bone tumor, is significantly influenced by the intricate interactions within its tumor microenvironment (TME), particularly involving neutrophils. This review delineates multifaceted roles of neutrophils, including tumor-associated neutrophils (TANs) and neutrophil extracellular traps (NETs), in osteosarcoma’s pathogenesis. TANs exhibit both pro- anti-tumor phenotypes, modulating growth immune evasion, while NETs facilitate cell adhesion, migration, immunosuppression. Clinically, neutrophil-related markers such as neutrophil-to-lymphocyte ratio (NLR) predict patient outcomes, highlighting potential for neutrophil-targeted therapies. Unraveling these complex crucial developing novel treatment strategies that harness TME to improve osteosarcoma management.

Language: Английский

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TRPM channels in human cancers: regulatory mechanism and therapeutic prospects

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Dec. 4, 2024

Abstract The transient receptor potential melastatin (TRPM) channel family has been previously implicated in various diseases, including those related to temperature sensing, cardiovascular health, and neurodegeneration. Nowadays, increasing evidence indicates that TRPM members also play significant roles types of cancers, exhibiting both pro- anti-tumorigenic functions. They are involved tumor cell proliferation, survival, invasion, metastasis, serving as diagnostic prognostic biomarkers for cancer. This paper begins by describing the structure physiological functions members. It then outlines their several common malignancies, pancreatic, prostate, colorectal, breast, brain cancer, melanoma. Subsequently, we focused on investigating specific mechanisms which tumorigenesis development from microenvironment (TME) intracellular signaling. channels not only transmit signals TME regulate functions, but mediate extracellular matrix remodeling, is conducive malignant transformation cells. Importantly, depend regulation inflow ions cells, participate key signaling pathways progression, such Wnt/β-catenin, MAPK, PI3K/AKT, p53, autophagy. Finally, summarize current strategies challenges targeting treatment, discuss feasibility combining targeted drugs with cancer immunotherapy.

Language: Английский

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