Influence of organ site and tumor cell type on MUC1-specific tumor immunity

• Published in: International immunology 2001-02, Vol.13 (2), p.233-240
• Main Authors: Morikane, Keita, Tempero, Richard M., Sivinski, Connie L., Kitajima, Shimichi, Gendler, Sandra J., Hollingsworth, Michael A.
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; CTL cytotoxic T lymphocyte; Female; Graft Rejection - immunology; Graft Rejection - pathology; Humans; Immunity, Cellular - genetics; Immunity, Cellular - immunology; immunological tolerance; Injections, Subcutaneous; Mice; Mice, Inbred C57BL; Mice, Transgenic; MUC-1 antigen; MUC1; Mucin-1 - immunology; Neoplasm Transplantation - immunology; Organ Specificity - genetics; Organ Specificity - immunology; orthotopic; Pancreas - immunology; Pancreas - pathology; pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - immunology; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Survival Analysis; Tumor Cells, Cultured - transplantation; tumor immunity
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/13.2.233

We investigated the influence of organ-specific parameters on tolerance and immunity to human MUC1. C57Bl/6 mice (wild-type) and C57Bl/6 transgenic for MUC1 (MUC1.Tg) were challenged in the pancreas with Panc02-MUC1, a C57Bl/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 Panc02-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 Panc02-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. Panc02-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.