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

Abstract

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.

Detection of BCR-ABL-Positive Cells in the Colostrum of a Pregnant Patient with Chronic Myeloid Leukemia

“…In animal models, the presence of numerous maternal cells or soluble antigens in breast milk could induce tolerance to maternal cells (7,8,13), while ingestion of tumor fragments could give the tumor cells a growth advantage (10)(11)(12). These results suggest that breast milk containing maternal leukemic cells, as well as normal cells, might facilitate tolerance to and promote growth of maternal leukemic cells transmitted to the infant during pregnancy.…”

“…Breast milk contains a number of maternal antigens and leukocytes. Another report in mice showed that oral feeding of tumor fragments could confer a growth advantage on, and induce immune tolerance to, tumor cells (10)(11)(12). These findings suggest that breast feeding after delivery could promote a survival advantage for and tolerance to maternal BCR-ABL-positive cells, in the event of their transmission to the infant.…”

Oral Tolerance to Cancer Can Be Abrogated by T Regulatory Cell Inhibition

“…It is likely that tumour Ags derived from tumour tissue shed into the intestine by foregut cancers would be processed by the gut associated lymphoid tissues (GALT), predominantly found in the proximal gastrointestinal tract, in a way reminiscent of Ags ingested by the mucosal immune system, thus creating a tumour Ag specific immune tolerance. We previously reported that orally administered fresh tumour tissue induced a tumour Ag specific non-cross-reactive immune tolerance with a consequent growth advantage for the cancer [4].…”

Local gene therapy of solid tumors with GM-CSF and B7-1 eradicates both treated and distal tumors

“…18 JBS is a negative variant for the large T antigen and was derived from the simian virus 40 (SV40)-transformed 3T3 cell line in our laboratory by Dr John Barrett. 19 The SV40 3T3 cell line is tumorigenic only in immunocompromised mice, for example, MF1 athymic nude mice, and not in the immunocompetent syngeneic Balb/C animal. The JBS cell line was developed from a tumor that occurred spontaneously in one of a panel of Balb/C mice that were inoculated with SV403T3 cells in doses equivalent to those found to be tumorigenic in the athymic mouse.…”

“…This tumor grows in immunocompetent Balb/C at the same rate as in athymic nude mice. 19 Vaccination strategies, using a diversity of approaches, schedules and cell treatments, failed to protect Balb/C mice from subsequent tumorigenic JBS challenges (Table 1). Thus, this cell is considered weakly or non-immunogenic.…”