2. Academic Validation
  3. The CHI3L1-neutrophil axis drives immune suppression and breast cancer metastatic dissemination

The CHI3L1-neutrophil axis drives immune suppression and breast cancer metastatic dissemination

  • JCI Insight. 2026 Feb 3;11(6):e199307. doi: 10.1172/jci.insight.199307.
Tarek Taifour 1 2,  Adéline Massé 2 3,  Yu Gu 2 3,  Virginie Sanguin-Gendreau 2,  Dongmei Zuo 2,  Bin Xiao 2,  Emilie Solymoss 1 2,  Yunyun Shen 2 3,  Hailey Proud 2 3,  Sherif Samer Attalla 2,  Vasilios Papavasiliou 2,  Nancy U Lin 4,  Melissa E Hughes 4,  Kalie Smith 4,  Chun Geun Lee 5 6,  Suchitra Kamle 5,  Josie Ursini-Siegel 1 3 7,  Jack A Elias 5,  Peter M Siegel 1 2 3,  Rinath Jeselsohn 4,  William J Muller 1 2 3
Affiliations

Affiliations

  • 1 McGill University, Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Montreal, Quebec, Canada.
  • 2 Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada.
  • 3 McGill University, Department of Biochemistry, Faculty of Medicine, Montreal, Quebec, Canada.
  • 4 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
  • 5 Brown University, Molecular Biology and Immunology, Providence, Rhode Island, USA.
  • 6 Hanyang University, Intercollege, Seoul, South Korea.
  • 7 Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
PMID: 41632530 DOI: 10.1172/jci.insight.199307
Abstract

Immunosuppression and metastasis are critical hallmarks of breast Cancer, often linked to poor patient outcomes. The secreted cytokine chitinase-3-like 1 (CHI3L1) is frequently overexpressed in breast Cancer samples and promotes an immunosuppressed tumor microenvironment. Notably, CHI3L1 expression is elevated in metastatic patient samples when compared with the matched primary breast tumor. To investigate its role in breast Cancer metastasis, we generated an inducible genetically engineered mouse model that overexpresses CHI3L1 in the mammary epithelium. Ectopic expression of CHI3L1 in the polyomavirus middle T (PyMT) mouse model of breast Cancer suppressed antitumor immune responses, accelerated mammary tumor onset, and enhanced lung metastasis. Mechanistically, elevated CHI3L1 expression in the mammary epithelium enhanced neutrophil recruitment, which subsequently degraded the extracellular matrix and increased the number of circulating tumor cells. These findings reveal a key mechanism driving metastatic dissemination and argue that therapeutically targeting Chi3l1 could enhance antitumor immunity and suppress metastasis.

Keywords

Breast cancer; Extracellular matrix; Immunology; Neutrophils; Oncology.

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