The GM-CSF-IRF5 signaling axis in eosinophils promotes antitumor immunity through activation of type 1 T cell responses.

Arnold, Isabelle C; Artola-Boran, Mariela; Gurtner, Alessandra; Bertram, Katrin; Bauer, Michael; Frangez, Ziva; Becher, Burkhard; Kopf, Manfred; Yousefi, Shida; Simon, Hans-Uwe; Tzankov, Alexandar; Müller, Anne (2020). The GM-CSF-IRF5 signaling axis in eosinophils promotes antitumor immunity through activation of type 1 T cell responses. Journal of experimental medicine, 217(12) Rockefeller University Press 10.1084/jem.20190706

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The depletion of eosinophils represents an efficient strategy to alleviate allergic asthma, but the consequences of prolonged eosinophil deficiency for human health remain poorly understood. We show here that the ablation of eosinophils severely compromises antitumor immunity in syngeneic and genetic models of colorectal cancer (CRC), which can be attributed to defective Th1 and CD8+ T cell responses. The specific loss of GM-CSF signaling or IRF5 expression in the eosinophil compartment phenocopies the loss of the entire lineage. GM-CSF activates IRF5 in vitro and in vivo and can be administered recombinantly to improve tumor immunity. IL-10 counterregulates IRF5 activation by GM-CSF. CRC patients whose tumors are infiltrated by large numbers of eosinophils also exhibit robust CD8 T cell infiltrates and have a better prognosis than patients with eosinophillow tumors. The combined results demonstrate a critical role of eosinophils in tumor control in CRC and introduce the GM-CSF-IRF5 axis as a critical driver of the antitumor activities of this versatile cell type.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Frangez, Ziva; Yousefi, Shida and Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1540-9538

Publisher:

Rockefeller University Press

Language:

English

Submitter:

Celine Joray

Date Deposited:

15 Oct 2020 11:02

Last Modified:

10 Mar 2021 08:58

Publisher DOI:

10.1084/jem.20190706

PubMed ID:

32970801

BORIS DOI:

10.7892/boris.146981

URI:

https://boris.unibe.ch/id/eprint/146981

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