ArticleApoptosis : an international journal on programmed cell death2025
The CXCL8-CXCR2 axis promotes M2 macrophage polarization in ovarian cancer via RASGRP4-mediated mTOR-STAT3 signaling.
Article in Apoptosis : an international journal on programmed cell death, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- ATF4 orchestrates cancer hallmarks: Stress adaptation, metabolic reprogramming and immune suppression.iScience · 2026Review
- Epicatechin suppresses cancer stem-like cell phenotype and radioresistance in non-small cell lung cancer via targeting CXCL8.Biology direct · 2026Article
- Selected Chemokines as Prognostic Biomarkers and Therapeutic Targets in Ovarian Cancer.Current issues in molecular biology · 2026Review
- Role of the STAT3 Signaling Pathway in Cell Proliferation and Inflammation in Psoriasis and Approaches for Targeted Therapies: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Inhibition of TLR4 enhances oxaliplatin chemotherapy sensitivity in esophageal squamous cell carcinoma by suppressing inflammation and glycolysis.BMC gastroenterology · 2026Article
- PEAK1 promotes prostate cancer progression and docetaxel resistance by mediating the polarization of tumor-associated macrophages.European journal of medical research · 2026Article
- Innate immune signaling-driven myeloid remodeling in cancer: inflammatory amplification, immune suppression, and therapeutic targeting.Frontiers in immunology · 2026Review
- Cervical lymph node response to 131I therapy in differentiated thyroid cancer using radiomics and clinical features.Frontiers in oncology · 2026Article
- CXCL8 Promotes the Progression of Vulvar Squamous Cell Carcinoma and Serves as a Potential Prognostic Biomarker.International journal of women's health · 2026Article
- PGE1 Suppresses the Expression of M2 Markers on Macrophages Through Prostaglandin Receptors.Cells · 2025Article
- Macrophages and neutrophils in ovarian cancer microenvironment.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
This study aimed to investigate whether CXCL8-CXCR2 axis in regulating M2 macrophage polarization via RASGRP4 related signaling in ovarian cancer. Data from The Cancer Genome Atlas (TCGA) database was used to assess the correlation between CXCR2 expression and M2 macrophage infiltration. THP-1 human monocytic cells were utilized to analyze the effects of CXCL8 on RASGRP4 expression and M2 polarization. In vivo experiments were conducted using xenograft models to evaluate the impact of CXCL8 and RASGRP4 on tumor growth and macrophage polarization. Among the CXCR2 co-expressed genes, RASGRP4 showed the highest positive correlation with M2 macrophage infiltration in ovarian cancer. Higher expression of RASGRP4 is associated with poorer progression-free survival in patients with serous ovarian cancer. CXCR2 knockdown or inhibition (using SB225002) reduced IL-8-induced upregulation of RASGRP4 mRNA and protein in THP-1 cells. Additionally, PLCβ2 silencing attenuated IL-8-induced RASGRP4 expression. Knockdown of RASGRP4 in THP-1 cells reduced M2 polarization, while overexpression restored it. The CXCL8-CXCR2 axis further enhances M2 polarization through RASGRP4-mediated mTOR-STAT3 signaling. In xenograft ovarian tumor models, knockdown of CXCL8, CXCR2, or RASGRP4 reduced tumor growth and M2 macrophage infiltration. In summary, the CXCL8-CXCR2 axis promotes M2 macrophage polarization via RASGRP4-mediated mTOR-STAT3 signaling in ovarian cancer. Targeting this pathway may be a promising therapeutic strategy to reprogram tumor-associated macrophages and enhance treatment efficacy.
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