Abstract
We investigated the influence of organ-specific parameters on tolerance and immunity to human MUC1. C57BI/6 mice (wild-type) and C57BI/6 transgenic for MUC1 (MUC1. Tg) were challenged in the pancreas with Panc02-MUC1, a C57B1/6-syngeneic pancreatic cancer cell line expressing human MUC1. Wild-type mice produced immune responses to MUC1 when presented on tumor cells growing in the pancreas; however, the responses to tumors in the pancreas were less effective than responses produced by tumor challenge at the s.c. site. Tumor immunity specific for MUC1 was produced in wild-type mice by two different procedures: (i) s.c. immunization of wild-type mice with a low dose of PancO2-MUC1 or (ii) adoptive transfer of spleen and lymph node cells harvested from wild-type mice previously immunized s.c. with Panc02-MUC1. This demonstrates that immune responses to MUC1 presented at the s.c. site can be detected and adoptively transferred. MUC1.Tg mice were immunologically tolerant to MUC1; however, some immunological protection against orthotopic challenge with PancO2-MUC1 was conferred by adoptive transfer of CD4+ and CD8+ T cells from wild-type mice. These results show that it is more difficult to produce immune responses to tumors growing at the pancreatic site than the s.c. site. PancO2-MUC1 cells growing in the pancreas were accessible to the immune system, and immune responses evoked by s.c. presentation of this molecule in wild-type mice were effective in rejecting tumor cells in the pancreas of both wild-type and MUC1.Tg mice. No effective anti -tumor immune responses against MUC1 were produced in MUC1.Tg mice.
Original language | English (US) |
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Pages (from-to) | 233-240 |
Number of pages | 8 |
Journal | International Immunology |
Volume | 13 |
Issue number | 2 |
DOIs | |
State | Published - 2001 |
Keywords
- Immunological tolerance
- MUC1
- Orthotopic
- Pancreatic cancer
- Tumor immunity
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology