Influence of organ site and tumor cell type on MUC1-specific tumor immunity.
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.
Morikane
K
K
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, NE 68198-6805, USA.
Tempero
R
R
Sivinski
C L
CL
Kitajima
S
S
Gendler
S J
SJ
Hollingsworth
M A
MA
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D007279:Injections, Subcutaneous; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000276:immunology*; D009368:Neoplasm Transplantation / Q000276:immunology; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010179:Pancreas / Q000276:immunology* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D014407:Tumor Cells, Cultured / Q000637:transplantation
D018396:Mucin-1