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CTLA4 blockade promotes vessel normalization in breast tumors via the accumulation of eosinophils
Author(s) -
Zheng Xichen,
Zhang Naidong,
Qian Long,
Wang Xuexiang,
Fan Peng,
Kuai Jiajie,
Lin Siyang,
Liu Changpeng,
Jiang Wen,
Qin Songbing,
Chen Haifeng,
Huang Yuhui
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32829
Subject(s) - blockade , eosinophil , infiltration (hvac) , medicine , cytotoxic t cell , immunology , breast cancer , cancer research , immune system , receptor , biology , cancer , in vitro , biochemistry , physics , asthma , thermodynamics
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.