Group 2 innate lymphoid cells promote TNBC lung metastasis via the IL-13-MDSC axis in a murine tumor model

• Published in: International immunopharmacology 2021-10, Vol.99, p.107924-107924, Article 107924
• Main Authors: Zhao, Na, Zhu, Wenwen, Wang, Jia, Liu, Weiwei, Kang, Longdan, Yu, Rui, Liu, Beixing
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Antibodies; Breast cancer; CD4 antigen; CD8 antigen; Cell Line, Tumor; Cell proliferation; Coculture Techniques; Cytokines - genetics; Cytokines - immunology; Depletion; Female; Gene expression; IL-13; ILC2s; Immunity, Innate; Immunoregulation; Interleukin 13; Interleukin-13 - immunology; Lung - immunology; Lung cancer; Lung metastasis; Lung Neoplasms - immunology; Lung Neoplasms - secondary; Lung nodules; Lungs; Lymphocytes; Lymphocytes - immunology; Lymphocytes T; Lymphoid cells; Mammary Neoplasms, Experimental - immunology; Mammary Neoplasms, Experimental - pathology; MDSCs; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Monoclonal antibodies; mRNA; Myeloid-Derived Suppressor Cells - immunology; Neutralization; Nodules; Receptors, Cytokine - genetics; Receptors, Cytokine - immunology; Suppressor cells; Survival; TNBC; Triple Negative Breast Neoplasms - immunology; Triple Negative Breast Neoplasms - pathology; Tumors
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2021.107924

•Pulmonary ILC2s can accelerate TNBC lung metastasis.•ILC2-accelerated TNBC lung metastasis depends on ILC2-derived IL-13.•The function of pulmonary MDSCs is regulated by ILC2-derived IL-13. Group 2 innate lymphoid cells (ILC2s) are reportedly associated with the progression of many tumors. However, the role of ILC2s in triple‐negative breast cancer (TNBC) lung metastasis remains unclear. In this study, we found that ILC2s may be a key element in the process of TNBC lung metastasis since the adoptive transfer of pulmonary ILC2s increased the numbers of metastatic lung nodules and reduced the survival of tumor-bearing mice. ILC2-promoted 4 T1 lung metastasis appears to be related to ILC2-derived IL-13. An expansion of IL-13-producing ILC2s and an elevated expression of IL-13 mRNA in pulmonary ILC2s were determined in tumor-bearing mice, in parallel with an increase in the levels of local IL-13 by ILC2 transfer. The neutralization of IL-13 reduced the increased pulmonary metastatic nodules and improved the decreased survival rate caused by ILC2-adoptive transfer. Interestingly, adoptive transfer of ILC2s elevated IL-13Ra1 expression in myeloid-derived suppressor cells (MDSCs). Treatment of ILC2-transferred tumor-bearing mice with anti-IL-13 antibodies significantly diminished the number of pulmonary MDSCs and inhibited MDSC activation. Moreover, when pulmonary MDSCs were cocultured with ILC2s in the presence of an anti-IL-13 mAb, the number and activation of MDSCs were reduced. Depletion of MDSCs may promote the proliferation of CD4+ T cells and CD8+ T cells, but reduce the expansion of regulatory T cells (Tregs) in the lungs of ILC2-transferred tumor-bearing mice. Our results suggest that pulmonary ILC2s may promote TNBC lung metastasis via the ILC2-derived IL-13-activated MDSC pathway.