Peripheral blood and tissue eosinophilia is a prominent feature in allergic diseases and helminth infections. In cancer patients, tumor-associated tissue eosinophilia is frequently observed. Tumor-associated tissue eosinophilia can be associated with a favorable prognosis, notably in colorectal carcinoma. However, underlying mechanisms of eosinophil contribution to antitumor responses are poorly understood. We have in this study investigated the direct interactions of human eosinophils with Colo-205, a colorectal carcinoma cell line, and show that eosinophils induce apoptosis and directly kill tumor cells. Using blocking Abs, we found that CD11a/CD18 complex is involved in the tumoricidal activity. Coculture of eosinophils with Colo-205 led to the release of eosinophil cationic protein and eosinophil-derived neurotoxin as well as TNF-α secretion. Moreover, eosinophils expressed granzyme A, which was released upon interaction with Colo-205, whereas cytotoxicity was partially inhibited by FUT-175, an inhibitor of trypsin-like enzymatic activity. Our data present the first demonstration, to our knowledge, that granzyme A is a cytotoxic mediator of the eosinophil protein arsenal, exerting eosinophil tumoricidal activity toward Colo-205, and provide mechanistic evidence for innate responses of eosinophil against tumor cells.

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Eosinophils are multifunctional leukocytes that are involved in innate and adaptive immune responses through the expression of various receptors and mediators. Previously, we showed that human eosinophils and T cells shared cytotoxic activities against tumor cells that involved the γ-δ TCR and cell–cell contact. In this study, we investigated the molecules involved in eosinophil–tumor cell interactions. Given the role of IL-18 in cell adhesion and in protecting against colon cancer, we evaluated its role in eosinophil-mediated cytotoxicity against Colo-205, a human colon carcinoma cell line. We found that human eosinophils exerted dose- and time-dependent tumoricidal activity against Colo-205 cells. Neutralization of IL-18 significantly reduced eosinophil-mediated Colo-205 apoptosis and inhibited cell–cell adhesion. Moreover, addition of rIL-18 led to upregulation of CD11a and ICAM-1 adhesion molecules, which were involved in the contact between eosinophils and Colo-205 cells. Our results indicated that IL-18 was involved in the eosinophil-mediated death of Colo-205 by facilitating contact between effector and target cells. These data underscored the involvement of an additional mediator in eosinophil-mediated antitumor cytotoxicity. Our findings support existing evidence that eosinophils could play a beneficial role in the context of colon cancer.