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 ki lling of breast cancer cells by autologous lymphocytes was examined in 26 p atients with breast cancer, significant tumour cell lysis was observed in 8 patients, whereas virtually no autologous tumour cell lysis was detected i n as many as 18 patients. In the patients who showed negligible tumour cell lysis, the autologous tumour cells expressed MUC1-related antigenic epitop es much more weakly than the tumour cells in the patients who exhibited str ong cytotoxicity (significant statistically at P < 0.0005-0.0045), suggesti ng that the unresponsiveness of cancer cells to CTLs observed in these pati ents was mainly due to loss of MUC1 expression or modulation of its antigen icity. A breast cancer cell line. NZK-1, established from one of the cytoto xicity-negative patients, did not express MUC1 and was resistant to killing by CTLs, while control breast cancer cell lines expressing MUC-1 were read ily killed by CTLs. Transfection of NZK-1 cells with MUC1 cDNA induced sign ificant lysis by autologous T-lymphocytes. These results supported the impo rtance of MUC1 mucin in autologous anti-tumour immunity, but suggested that the major escape mechanism of tumour cells from autologous T-lymphocytes i s the loss and/or modulation of MUC1 antigenicity on tumour cells, which wo uld limit the effectiveness of possible immunotherapy designed to target th e MUC1 mucin. (C) 2001 Cancer Research Campaign.