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

Keita Morikane, Richard M. Tempero, Connie L. Sivinski, Shimichi Kitajima, Sandra J. Gendler, Michael A. Hollingsworth

Research output: Contribution to journalArticle

16 Scopus citations

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 languageEnglish (US)
Pages (from-to)233-240
Number of pages8
JournalInternational Immunology
Volume13
Issue number2
DOIs
StatePublished - Jan 1 2001

Keywords

  • Immunological tolerance
  • MUC1
  • Orthotopic
  • Pancreatic cancer
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Morikane, K., Tempero, R. M., Sivinski, C. L., Kitajima, S., Gendler, S. J., & Hollingsworth, M. A. (2001). Influence of organ site and tumor cell type on MUC1-specific tumor immunity. International Immunology, 13(2), 233-240. https://doi.org/10.1093/intimm/13.2.233