Oral immune tolerance to tumor specific antigens may confer growth advantage to esophageal and gastric cancers

Oral administration of antigens induces antigen-specific systemic immune tolerance (Oral Tolerance). We postulate that the poorer prognosis of foregut cancers might, in part be explained by the systemic immune tolerizing effect of tumor specific antigens shed into and processed by the gut immune system thus conferring a growth advantage specific to individual cancers. Immunocompetent Balb/c mice were fed by gavage, either tumor tissue (JBS/CarB) in phosphate buffered saline (PBS) or PBS alone, daily for 14 days. On day 15 either subcutaneous tumors were induced or animals were immunized with cells in adjuvant. JBS tumors appeared earlier and grew faster in the JBS tumor fed mice than in either the PBS (P = 0.025) or CarB (P = 0.168) fed animals. The delayed type hypersensitivity response in tolerized mice was significantly abrogated (P < 0.01) compared to controls. These experiments demonstrate antigen specific oral immune tolerance for tumors, which is reflected in a faster growth rate and impaired delayed type hypersensitivity response. Similar mechanisms may be operational in human esophagogastric malignancy and may in part explain their poorer outcome.