ArticleCancer cell international2022
Crosstalk between tumor-associated macrophages and tumor cells promotes chemoresistance via CXCL5/PI3K/AKT/mTOR pathway in gastric cancer.
Article in Cancer cell international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Unraveling the role of M2 TAMs in ovarian cancer dynamics: a systematic review.Journal of translational medicine · 2025Pooled it
- Phase 2 trial of perioperative chemo-immunotherapy for gastro-esophageal adenocarcinoma: The role of M2 macrophage landscape in predicting response.Cell reports. Medicine · 2025Trial
- Opioid-free anesthesia attenuates perioperative immunosuppression by regulating macrophages polarization in gastric cancer patients treated with neoadjuvant PD-1 inhibitor.Frontiers in immunology · 2024Trial
- Macrophage Trogocytosis of Tumor Cells Drives the Immunosuppression of Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Anticancer Effects of Fluphenazine Alone and in Combination with Cisplatin in Gastric Cancer Cells and a Mouse Xenograft Model.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Impact of spatial distribution of M2 macrophages on prognosis and neoadjuvant chemotherapy resistance in gastric cancer.Journal of gastrointestinal oncology · 2026Article
- The vessels encapsulating tumor clusters (VETC) pattern is a negative predictor for first-line immune checkpoint inhibitors alone in unresectable hepatocellular carcinoma.Journal of gastroenterology · 2026Article
- Gastric Cancer Organoids: Mechanistic Insights, Drug Discovery, and Translational Advances in Precision Medicine.Journal of gastric cancer · 2026Review
- Tumor-stromal crosstalk and macrophage enrichment are associated with chemotherapy response in bladder cancer.FEBS open bio · 2026Article
- Naringenin, a Food-Derived Flavanone, Suppresses ITGA11-Associated Gastric Cancer Progression via the FAK/PI3K/AKT/mTOR Axis.Cancers · 2026Article
- Combinational studies of BOLD-100/KP1339 with established chemotherapeutics in gastrointestinal multicellular tumor spheroids.Cancer chemotherapy and pharmacology · 2026Article
- SPINK4 affected M2 macrophage polarization to promote colorectal cancer malignant phenotype by PI3K/AKT pathway.BMC cancer · 2026Article
- Homoharringtonine suppresses gastric cancer progression by targeting PI3K/ AKT/FOXO pathway and impairing the GSH-GPX4 antioxidant axis.Cancer chemotherapy and pharmacology · 2026Article
- M2-polarized tumor-associated macrophages as key orchestrators of gastric cancer pathogenesis and therapeutic resistance.Discover oncology · 2026Review
- Targeting Prolyl 3-hydroxylase 1 inhibits pancreatic cancer progression and macrophage immunity.Nature communications · 2026Article
- Nutritional modulation of metabolic signaling within the tumor microenvironment for cancer therapy.Molecular and cellular biochemistry · 2026Review
- CD44 upregulation in chronic liver disease marks the transition to hepatocellular carcinoma and portends poor prognosis.British journal of cancer · 2026Article
- Traditional Chinese medicine modulates tumor-associated macrophages to suppress gastric cancer progression: mechanisms and therapeutic potential.Frontiers in oncology · 2026Review
- Yi-qi-hua-yu-jie-du Decoction Inhibits Gastric Cancer Progression by Inducing Tumor-Associated Macrophage Polarization via Modulating PP2A Enzyme Activity to Mediate the PI3K/AKT/NF-κB Axis.Journal of inflammation research · 2026Article
- Chemoresistance in the era of immunotherapy: challenges and novel combinatorial strategies for digestive system tumors.Frontiers in immunology · 2026Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
background5-fluorouracil (5-FU)-based chemotherapy regimen has been widely used for the treatment of gastric cancer, but meanwhile the development of chemotherapeutic resistance remains a major clinical challenge. Tumor microenvironment (TME) frequently correlates with the development of chemoresistance in human cancer. As a major component of TME, the role of tumor-associated macrophages (TAMs) in the chemoresistance of gastric cancer has not been fully elucidated.
methodsImmunohistochemistry (IHC) was applied to detect the density of TAMs in clinical samples of 103 patients with gastric cancer who had undergone 5-FU-based neoadjuvant chemotherapy. 5-FU-resistant gastric cell lines MKN45-R and HGC27-R were established, macrophages were then separately co-cultured with MKN45-R, HGC27-R cells and their parental cells. The effect of gastric cancer cells on the polarization of macrophages, the biological function of M2-polaried macrophages and the mechanism for promoting 5-FU-resistance were investigated. Then the correlation between the expression of CXC motif chemokine ligand 5 (CXCL5) and the infiltration of hemoglobin scavenger receptor (CD163) positive and mannose receptor (CD206) positive macrophages was analyzed, the prognostic value of CXCL5 expression in clinical samples was further explored.
resultsThe high infiltration of macrophages marked by CD68 in gastric cancer samples was significantly associated with the resistance of gastric cancer to chemotherapy. Gastric cancer cells could modulate macrophages to M2-like polarization through indirect co-culture, and chemoresistant cells were more efficient in inducing macrophages polarization to M2 phenotype. Co-culturing M2-polarized macrophages in turn enhanced 5-FU-resistance of gastric cancer cells, and it was further verified that CXCL5 derived from M2-polarized macrophages promoted chemoresistance through activing the PI3K/AKT/mTOR pathway. Besides, high level of CXCL5 could recruit monocytes to form more M2-polarized macrophages. Clinically, high expression of CXCL5 in gastric cancer samples was associated with the high infiltration of CD163 positive macrophages and CD206 positive macrophages, and patients with high expression of CXCL5 presented lower overall survival (OS) rates than those with low expression of CXCL5.
conclusionInteraction between TAMs and gastric cancer cells promoted chemoresistance in gastric cancer via CXCL5/PI3K/AKT/mTOR pathway. Thus, targeting TAMs and blocking the cell-cell crosstalk between TAMs and gastric cancer cells may represent prospective therapeutic strategies for patients with gastric cancer.
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