Breast cancer-associated antigen, DF3/MUC1, induces apoptosis of activated human T cells.
Given the plethora of well-documented breast carcinoma-associated antigens in humans including MAGE-1, -2 and -3, mutated p53, p21ras, HER-2/neu and DF3/MUC-1, coupled with evidence that humoral and cytotoxic T-cell responses against these antigens exist, the central dilemma facing tumor immunologists is why the host immune response is so inefficient. One possibility is that tumor cells themselves are either inefficient or ineffective antigen-presenting cells (APCs). The failure of tumor cells to function as APCs may be due to their inability to process and present the antigen, the absence or insufficient numbers of adhesion and costimulatory molecules or, potentially, the secretion of inhibitory cytokines. Therefore, we sought to determine whether human breast cancer cell lines could function as APCs and, if not, to identify mechanism(s) responsible for this defect. Here, we show that human breast cancer cell lines fail to present alloantigen. This defect does not reside in their inherent capacity to present antigen but rather is due to apoptosis of activated T cells induced by exposure to the breast carcinoma-associated mucin antigen, DF3/MUC1. These results support the hypothesis that DF3/MUC1 may contribute to the paucity of clinically significant anticarcinoma-specific immune responses.
Gimmi
C D
CD
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Morrison
B W
BW
Mainprice
B A
BA
Gribben
J G
JG
Boussiotis
V A
VA
Freeman
G J
GJ
Park
S Y
SY
Watanabe
M
M
Gong
J
J
Hayes
D F
DF
Kufe
D W
DW
Nadler
L M
LM
D016475:3T3 Cells; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000494:pharmacology; D015295:Antigens, Tumor-Associated, Carbohydrate; D017209:Apoptosis / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000276:immunology*; D002277:Carcinoma / Q000276:immunology*; D005260:Female; D005347:Fibroblasts; D015809:HLA-DR7 Antigen / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D018122:B7-1 Antigen; D014408:Biomarkers, Tumor; D015809:HLA-DR7 Antigen; D008934:Mitogens; D010835:Phytohemagglutinins; C057387:mucinous carcinoma-associated antigen