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ResearchIn-Press PreviewImmunologyOncology Open Access | 10.1172/jci.insight.199307

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

Tarek Taifour,1 Adéline Massé,2 Yu Gu,2 Virginie Sanguin-Gendreau,2 Dongmei Zuo,2 Bin Xiao,2 Emilie Solymoss,1 Yunyun Shen,2 Hailey Proud,2 Sherif Samer Attalla,2 Vasilios Papavasiliou,2 Nancy U. Lin,3 Melissa E. Hughes,3 Kalie Smith,3 Chun Geun Lee,4 Suchitra Kamle,4 Josie Ursini-Siegel,1 Jack A. Elias,4 Peter M. Siegel,1 Rinath Jeselsohn,3 and William J. Muller1

1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

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1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

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1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

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1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

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1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

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1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

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1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

Find articles by Solymoss, E. in: PubMed | Google Scholar

1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

Find articles by Shen, Y. in: PubMed | Google Scholar

1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

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1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

Find articles by Attalla, S. in: PubMed | Google Scholar |

1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

Find articles by Papavasiliou, V. in: PubMed | Google Scholar

1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

Find articles by Lin, N. in: PubMed | Google Scholar

1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

Find articles by Hughes, M. in: PubMed | Google Scholar

1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

Find articles by Smith, K. in: PubMed | Google Scholar

1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

Find articles by Lee, C. in: PubMed | Google Scholar |

1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

Find articles by Kamle, S. in: PubMed | Google Scholar |

1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

Find articles by Ursini-Siegel, J. in: PubMed | Google Scholar

1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

Find articles by Elias, J. in: PubMed | Google Scholar |

1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

Find articles by Siegel, P. in: PubMed | Google Scholar

1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

Find articles by Jeselsohn, R. in: PubMed | Google Scholar

1Division of Experimental Medicine, Department of Medicine, Faculty of Medic, McGill University, Montreal, Canada

2Rosalind and Morris Goodman Cancer Institute, Montreal, Canada

3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States of America

4Molecular Biology and Immunology, Brown University, Providence, United States of America

Find articles by Muller, W. in: PubMed | Google Scholar

Published February 3, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.199307.
Copyright © 2026, Taifour et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published February 3, 2026 - Version history
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Abstract

Immunosuppression and metastasis are critical hallmarks of breast cancer, often linked to poor patient outcomes. The secreted cytokine chitinase-3 like 1 (CHI3L11) is frequently overexpressed in breast cancer samples and promotes an immunosuppressed tumor microenvironment. Notably, CHI3L1 expression is elevated in metastatic patient samples when compared to the matched primary breast tumor. To investigate its role in breast cancer metastasis, we generated an inducible Genetically Engineered Mouse Model (GEMM) that overexpresses CHI3L1 in the mammary epithelium. Ectopic expression of CHI3L1 in the Polyomavirus Middle T (PyMT) mouse model of breast cancer suppressed anti-tumor 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 anti-tumor immunity and suppress metastasis.

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  • Version 1 (February 3, 2026): In-Press Preview
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