Activated eosinophils exert antitumorigenic activities in colorectal cancer

Hadar Reichman, Michal Itan, Perri Rozenberg, Tal Yarmolovski, Eli Brazowski, Chen Varol, Nathan Gluck, Shiran Shapira, Nadir Arber, Udi Qimron, Danielle Karo-Atar, James J. Lee, Ariel Munitz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Immunotherapies targeting T lymphocytes are revolutionizing cancer therapy but only benefit a subset of patients, especially in colorectal cancer. Thus, additional insight into the tumor microenvironment (TME) is required. Eosinophils are bone marrow–derived cells that have been largely studied in the context of allergic diseases and parasite infections. Although tumor-associated eosinophilia has been described in various solid tumors including colorectal cancer, knowledge is still missing regarding eosinophil activities and even the basic question of whether the TME promotes eosinophil recruitment without additional manipulation (e.g., immunotherapy) is unclear. Herein, we report that eosinophils are recruited into developing tumors during induction of inflammation-induced colorectal cancer and in mice with the Apc min/þ genotype, which develop spontaneous intestinal adenomas. Using adoptive transfer and cytokine neutralization experiments, we demonstrate that the TME supported prolonged eosinophil survival independent of IL5, an eosinophil survival cytokine. Tumor-infiltrating eosinophils consisted of degranulating eosinophils and were essential for tumor rejection independently of CD8 þ T cells. Transcriptome and proteomic analysis revealed an IFNg-linked signature for intratumoral eosinophils that was different from that of macrophages. Our data establish antitumorigenic roles for eosinophils in colorectal cancer. These findings may facilitate the development of pharmacologic treatments that could unleash antitumor responses by eosinophils, especially in colorectal cancer patients displaying eosinophilia.

Original languageEnglish
Pages (from-to)388-400
Number of pages13
JournalCancer immunology research
Volume7
Issue number3
DOIs
StatePublished - Mar 2019

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