Modulation of MUC1 mucin as an escape mechanism of breast cancer cells from autologous cytotoxic T-lymphocytes.
MUC1 mucin is known to serve as a target molecule in the killing of breast cancer cells by cytotoxic T-lymphocytes (CTLs). We searched for a possible mechanism allowing tumour cells to escape from autologous CTLs. When the killing of breast cancer cells by autologous lymphocytes was examined in 26 patients with breast cancer, significant tumour cell lysis was observed in 8 patients, whereas virtually no autologous tumour cell lysis was detected in as many as 18 patients. In the patients who showed negligible tumour cell lysis, the autologous tumour cells expressed MUC1-related antigenic epitopes much more weakly than the tumour cells in the patients who exhibited strong cytotoxicity (significant statistically at P< 0.0005-0.0045), suggesting that the unresponsiveness of cancer cells to CTLs observed in these patients was mainly due to loss of MUC1 expression or modulation of its antigenicity. A breast cancer cell line, NZK-1, established from one of the cytotoxicity-negative patients, did not express MUC1 and was resistant to killing by CTLs, while control breast cancer cell lines expressing MUC-1 were readily killed by CTLs. Transfection of NZK-1 cells with MUC1 cDNA induced significant lysis by autologous T-lymphocytes. These results supported the importance of MUC1 mucin in autologous anti-tumour immunity, but suggested that the major escape mechanism of tumour cells from autologous T-lymphocytes is the loss and/or modulation of MUC1 antigenicity on tumour cells, which would limit the effectiveness of possible immunotherapy designed to target the MUC1 mucin.
Kontani
K
K
Program of Molecular Pathology, Department of Breast Surgery, Aichi Cancer Center, Nagoya, Japan.
Taguchi
O
O
Narita
T
T
Izawa
M
M
Hiraiwa
N
N
Zenita
K
K
Takeuchi
T
T
Murai
H
H
Miura
S
S
Kannagi
R
R
D000940:Antigenic Variation; D001943:Breast Neoplasms / Q000276:immunology*; D016923:Cell Death; D002470:Cell Survival; D018076:DNA, Complementary; D000939:Epitopes; D006801:Humans; D016219:Immunotherapy, Adoptive; D018396:Mucin-1 / Q000096:biosynthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D000939:Epitopes; D018396:Mucin-1