Eosinophils display anti-tumorigenic activities in mucosal sites

Over the past decade,the roles of various cells in the tumor microenvironment (TME) have been gradually elucidated; however, certain cells still remain in near-complete obscurity. Among these cells, our lack of knowledge regarding the role of eosinophils is highly surprising especially given the fact that tumor-associated eosinophilia has been first described more than 120 years ago, and that eosinophilia is frequently observed in many types of cancer. Interestingly, previous studies have shown that eosinophils can display either pro- or antitumorigenic functions, leading to controversy about their role. Nonetheless, most of the experimental data assessing the activity of eosinophils in cancer have been gathered using tumor cell lines that secrete eosinophil-promoting cytokines, genetically modified tumors that polarize a type 2 cytokine environment, responses to immunotherapy, or in the absence of T regulatory cells. Thus, translation of such data into human disease difficult.

To overcome previous caveats, we study eosinophils in cancer with experimental models that fulfilled three conditions: a) Tumor types with clinically reported data on increased tumor-infiltrating eosinophilia; b) tumor development occurs in an anatomically relevant tissue for eosinophils; and c) Tumor progression occurs gradually, allowing eosinophils to adapt to the TME. Employing these criteria led us to investigate eosinophils cancers that occur in mucosal tissue. We demonstrate potent non-redundant anti-tumorigenic activities for eosinophils in colorectal cancer and lung metastasis. Eosinophil-associated receptors as well as the role of eosinophils in the TME will be discussed.