Open AccessDifferential effector mechanisms induced by vaccination with MUC1 DNA in the rejection of colon carcinoma growth at orthotopic sites and metastases
Author(s) -
Sugiura Daisuke,
Aida Satoshi,
DendaNagai Kaori,
Takeda Kazuyoshi,
KamataSakurai Mika,
Yagita Hideo,
Irimura Tatsuro
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.00967.x
Subject(s) - metastasis , fas ligand , cancer research , cd8 , tumor necrosis factor alpha , immune system , biology , immunology , colorectal cancer , in vivo , effector , dna vaccination , cancer , medicine , apoptosis , programmed cell death , immunization , biochemistry , genetics , microbiology and biotechnology
The effects of MUC1 DNA vaccination on the orthotopic growth and liver metastasis of colon carcinoma cells were investigated in mice. Vaccination with MUC1 DNA resulted in immune responses that were effective in suppressing mouse colon carcinoma cells transfected with MUC1 cDNA. CD4 + T cells but not CD8 + T cells mediated this antitumor response as shown by the in vivo depletion of lymphocyte subpopulations with the use of anti‐CD4 or anti‐CD8 antibody. The effects of neutralizing antibodies in vivo revealed that the predominant effector molecule in preventing orthotopic tumor growth was FasL, whereas the effector molecule effective in preventing liver metastasis was tumor necrosis factor‐α. Colon carcinoma cells isolated from tumors growing in the ceca, spleens, and livers were shown to be equally sensitive to FasL and tumor necrosis factor‐α. The results strongly suggest that elimination of tumor cells initiated by DNA vaccination in the present protocol is mediated by antigen‐specific CD4 + T cells and the effector mechanisms in the cecum and in the liver are distinct due to a unique organ microenvironment. ( Cancer Sci 2008; 99: 2477–2484)