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Updated: Aug 18, 2025

The Use of Mouse Mammary Tumor Cells in an In Vitro Invasion Assay as a Measure of Oncogenic Cell Behavior
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Published on: June 12, 2019

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CXCL9 influences the tumor immune microenvironment by stimulating JAK/STAT pathway in triple-negative breast cancer

Lei Wu1,2,3, Shengnan Sun1,2, Fei Qu4

  • 1Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People's Republic of China.

Cancer Immunology, Immunotherapy : CII
|December 6, 2022
PubMed

Insights

This study identifies CXCL9 in M1 macrophages as a potential biomarker for triple-negative breast cancer (TNBC) prognosis and immunotherapy effectiveness. CXCL9 influences the tumor microenvironment by impacting macrophage differentiation and JAK/STAT signaling.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Triple-negative breast cancer (TNBC) presents a poor prognosis and limited treatment options.
  • Immunotherapy offers a promising therapeutic avenue for TNBC.
  • Understanding the tumor microenvironment is crucial for developing effective TNBC treatments.

Purpose of the Study:

  • To investigate the role of macrophage subtypes and their communication in TNBC.
  • To identify potential biomarkers for prognosis and immunotherapy response in TNBC.
  • To elucidate the molecular mechanisms involving CXCL9 in the TNBC tumor microenvironment.

Main Methods:

  • Single-cell RNA sequencing was employed to analyze TNBC.
  • Intercellular communication networks and signaling pathways (MHC-II, JAK/STAT) were investigated.
  • Gene Set Enrichment Analysis (GSVA) and Western blot were utilized to assess pathway activity and protein expression.

Main Results:

  • Highly expressed CXCL9 was detected in M1 macrophages within TNBC.
  • M1 macrophages demonstrated potential for differentiation into M2 macrophages, with decreasing CXCL9 expression during this process.
  • CXCL9 was significantly enriched in the MHC-II and JAK/STAT signaling pathways, and its overexpression promoted JAK1/STAT2 expression.

Conclusions:

  • CXCL9 serves as a potential clinical biomarker for predicting prognosis and immunotherapy efficacy in TNBC patients.
  • CXCL9 modulates the tumor microenvironment by influencing macrophage polarization and activating the JAK/STAT pathway.
  • These findings highlight CXCL9 as a key player in TNBC pathogenesis and a potential therapeutic target.
Keywords:
CXCL9ImmunotherapyMacrophagesSingle-cell RNA sequencingTriple-negative breast cancer

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