Human eosinophils exert TNF-α and granzyme A-mediated tumoricidal activity toward colon carcinoma cells.
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.
INSERM Unité 547, Institut Fédératif de Recherche 142, Lille, France.
Fanny
F
Legrand
Virginie
V
Driss
Marie
M
Delbeke
Sylvie
S
Loiseau
Emmanuel
E
Hermann
David
D
Dombrowicz
Monique
M
Capron
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D001550:Benzamidines; D040881:CD11a Antigen / Q000276:immunology / Q000378:metabolism; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism; D004802:Eosinophilia / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000201:enzymology* / Q000378:metabolism; D053804:Granzymes / Q000276:immunology* / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate; D014361:Trypsin Inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D001550:Benzamidines; D040881:CD11a Antigen; D018821:CD18 Antigens; D006146:Guanidines; D014361:Trypsin Inhibitors; D014409:Tumor Necrosis Factor-alpha; D053804:Granzymes; C032855:nafamostat