CTLA4 blockade promotes vessel normalization in breast tumors via the accumulation of eosinophils.
Int J Cancer
; 146(6): 1730-1740, 2020 03 15.
Article
en En
| MEDLINE
| ID: mdl-31840816
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Eosinófilos
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Antígeno CTLA-4
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Antineoplásicos Inmunológicos
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Neoplasias
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Neovascularización Patológica
Tipo de estudio:
Prognostic_studies
Límite:
Female
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Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article