Cancer-associated MUC1 mucin inhibits human T-cell proliferation, which is reversible by IL-2.
A number of adenocarcinomas abundantly express and secrete underglycosylated MUC1 mucin. Underglycosylation exposes tandem repeat peptide sequences on cancer-associated MUC1 mucin that are normally cryptic. High levels of MUC1 mucin are correlated with a poor prognosis and immunosuppression in adenocarcinoma patients. In this report we show that cancer-associated MUC1 mucin, affinity-purified from ascites fluids of cancer patients, and synthetic tandem repeats of MUC1 mucin core peptide can suppress human T-cell proliferative responses. This MUC1 mucin-induced suppression of T-cell responses can be reversed by the addition of exogenous IL-2 or anti-CD28 monoclonal antibody. These results are consistent with other studies showing that lymphocytes present in the vicinity of tumor cells are anergic and can be reactivated with exogenous interleukin-2. Overcoming MUC1 mucin-induced immunosuppression with IL-2 combined with active specific immunotherapy might be an effective immunotherapeutic strategy against human adenocarcinomas.
Agrawal
B
B
Biomira, Inc., Edmonton, AB, Canada.
Krantz
M J
MJ
Reddish
M A
MA
Longenecker
B M
BM
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D017209:Apoptosis; D001202:Ascitic Fluid; D018106:CD28 Antigens / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D016685:Mitomycin / Q000494:pharmacology; D018396:Mucin-1 / Q000302:isolation & purification / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018106:CD28 Antigens; D007376:Interleukin-2; D018396:Mucin-1; D016685:Mitomycin; D007371:Interferon-gamma