CTLA4 blockade promotes vessel normalization in breast tumors via the accumulation of eosinophils

Xichen Zheng, Naidong Zhang, Long Qian, Xuexiang Wang, Peng Fan, Jiajie Kuai, Siyang Lin, Changpeng Liu, Wen Jiang, Songbing Qin, Haifeng Chen, Yuhui Huang

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Immune checkpoint blockade (ICB) has shown long-term survival benefits, but only in a small fraction of cancer patients. Recent studies suggest that improved vessel perfusion by ICB positively correlates with its therapeutic outcomes. However, the underlying mechanism of such a process remains unclear. Here, we show that anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) treatment-induced tumor vessel normalization was accompanied by an increased infiltration of eosinophils into breast tumors. Eosinophil accumulation was positively correlated with the responsiveness of a breast tumor to anti-CTLA4 therapy. Depletion of eosinophils subsequently negated vessel normalization, reduced antitumor immunity and attenuated tumor growth inhibition by anti-CTLA4 therapy. Moreover, intratumoral accumulation of eosinophils relied on T lymphocytes and interferon γ production. Together, these results suggest that eosinophils partially mediate the antitumor effects of CTLA4 blockade through vascular remodeling. Our findings uncover an unidentified role of eosinophils in anti-CTLA4 therapy, providing a potential new target to improve ICB therapy and to predict its efficacy.

Original languageEnglish (US)
Pages (from-to)1730-1740
Number of pages11
JournalInternational Journal of Cancer
Volume146
Issue number6
DOIs
StatePublished - Mar 15 2020

Keywords

  • anti-CTLA4 therapy
  • breast cancer
  • eosinophils
  • tumor vessel normalization

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'CTLA4 blockade promotes vessel normalization in breast tumors via the accumulation of eosinophils'. Together they form a unique fingerprint.

  • Cite this

    Zheng, X., Zhang, N., Qian, L., Wang, X., Fan, P., Kuai, J., Lin, S., Liu, C., Jiang, W., Qin, S., Chen, H., & Huang, Y. (2020). CTLA4 blockade promotes vessel normalization in breast tumors via the accumulation of eosinophils. International Journal of Cancer, 146(6), 1730-1740. https://doi.org/10.1002/ijc.32829