Cancer-associated MUC1 mucin inhibits human T-cell proliferation, which is reversible by IL-2

Nat Med. 1998 Jan;4(1):43-9. doi: 10.1038/nm0198-043.


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.

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / immunology
  • Antigens, CD / physiology
  • Apoptosis
  • Ascitic Fluid
  • CD28 Antigens / immunology
  • CD28 Antigens / physiology*
  • Cells, Cultured
  • Chromatography, Affinity
  • Coculture Techniques
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / pharmacology*
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Culture Test, Mixed
  • Mitomycin / pharmacology
  • Mucin-1 / isolation & purification
  • Mucin-1 / pharmacology*
  • Ovarian Neoplasms / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*


  • Antibodies, Monoclonal
  • Antigens, CD
  • CD28 Antigens
  • Interleukin-2
  • Mucin-1
  • Mitomycin
  • Interferon-gamma