Human Eosinophils Exert TNF-α and Granzyme A-Mediated Tumoricidal Activity toward Colon Carcinoma Cells

Abstract

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.

Peritumoral eosinophils predict recurrence in colorectal cancer

“…An enhanced accumulation of tumorassociated eosinophils has also been observed when tumor cells were transfected with interleukin (IL)-5, whereas eosinophil-deficient IL-5/CCL11 ( À / À ) mice have been demonstrated to enable augmented tumorigenicity in xenograft models. 28 Tumoricidal activation and degranulation of eosinophils seem to depend on stable contacts with colorectal cancer 29 Reports from immunotherapeutic approaches in patients with epithelial tumors suggest that the accumulation and activity of eosinophils might represent an important mechanism of action. Efficacy of treatment with recombinant IL-2 in advanced cancers was associated with greater numbers of peritumoral eosinophils.…”

Eosinophilic biomarkers for detection of acute exacerbation of chronic obstructive pulmonary disease with or without pulmonary embolism

“…ECP has various biological activities, including antibacterial, antiviral, antiparasitic and neurotoxic functions, and it contributes to the regulation of fibroblast activity (21). ECP also induces airway mucus secretion and interacts with the coagulation and complement systems (22,23). Fiorini et al (24) concluded that serum ECP levels increased during AECOPD.…”

Associations between Atopic Dermatitis and Risk of Gastric Cancer: A Nationwide Population-based Study

“…27 There is mounting evidence that suggests that eosinophils and immunoglobulin E may play important roles in the protection against cancer development through activities associated with tumor cell cytotoxicity and tumor suppression. [28][29][30] Conversely, chronic inflammation increases the susceptibility of the affected organs to cancer, which may explain higher risks of lung cancer among patients with asthma and nasal cavity cancer among patients with allergic rhinitis. 8,17,31 Another explanation for the association between allergic disease and gastric cancer could be the inverse relationship between allergic disease and H. pylori infection, which is the most important risk factor for gastric cancer.…”