Emerging Roles For Eosinophils in the Tumor Microenvironment

Immunotherapies targeting T lymphocytes are revolutionizing cancer therapy yet they only benefit a subset of patients, especially in colorectal cancer (CRC). Thus, knowledge regarding additional cells in the tumor microenvironment (TME) is urgently required. Eosinophils are bone marrow-derived cells that have been largely studied in the context of allergic diseases and parasite infections. Despite the fact that tumor-associated eosinophilia has been described in various solid tumors including CRC, fundamental knowledge is still missing regarding their 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 swiftly recruited into developing tumors during induction of inflammation-induced CRC and in Apc^min/+ mice, which develop spontaneous intestinal adenomas. Using adoptive transfer and cytokine neutralization experiments, we demonstrate that the TME supported prolonged eosinophil survival independent of IL-5, a key eosinophil survival cytokine. Tumor-infiltrating eosinophils consisted of degranulating eosinophils and were essential for tumor rejection independently of CD8⁺T cells. Transcriptome and proteomic analysis revealed a functionally distinct IFN-g-linked signature for intratumoral eosinophils that was noticeably different from that of macrophages. Our data establish key anti-tumorigenic roles for eosinophils in CRC. These findings may facilitate the development of new pharmacological treatments unleashing anti-tumor responses by eosinophils especially in CRC patients displaying eosinophilia.