MUC1-specific anti-tumor responses: Molecular requirements for CD4-mediated responses

Michelle L. VanLith, Karl G. Kohlgraf, Connie L. Sivinski, Richard M Tempero, Michael A Hollingsworth

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

MUC1 was first defined as a tumor antigen in the late 1980s, yet little is known about the types of immune responses that mediate rejection of MUC1+ tumors in vivo. MUC1-specific antibodies, Th cells and cytotoxic T cells can be detected in patients with different adenocarcinomas, yet these tumors usually progress. Thus, there is a need to better understand the in vivo mechanisms of antigen-specific tumor rejection. To characterize the nature of MUC1-specific immune responses in vivo, rejection of a MUC1-expressing melanoma tumor line (B16.MUC1) was evaluated in mice lacking specific T cell subsets, cytokines, co-stimulatory molecules or molecular effectors of cytolytic pathways. Results demonstrated that rejection of the B16.MUC1 tumor cell line was primarily mediated by CD4+ T cells, and required Fas ligand, lymphotoxin-α, CD40, CD40 ligand and CD28, but not perforin, γδ T cells, IL-4, IL-10, IL-12 or tumor necrosis factor receptor-1. Depletion of NK cells demonstrated that NK cells might also contribute to MUC1 immunity in the B16.MUC1 tumor model. These results demonstrated that the immune response generated against MUC1 does not fit the type 1 or 2 model described for many immune responses. Additionally, multiple cytolytic mechanisms are required for B16.MUC1 rejection.

Original languageEnglish (US)
Pages (from-to)873-882
Number of pages10
JournalInternational Immunology
Volume14
Issue number8
StatePublished - Aug 29 2002

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Neoplasm Antigens
T-Lymphocytes
Natural Killer Cells
Neoplasms
Lymphotoxin-alpha
Perforin
CD40 Ligand
Fas Ligand Protein
Tumor Necrosis Factor Receptors
T-Lymphocyte Subsets
Interleukin-12
Tumor Cell Line
Interleukin-4
Interleukin-10
Immunity
Melanoma
Adenocarcinoma
Cytokines
Antibodies

Keywords

  • Cytokines
  • MUC1
  • T cells
  • Tumor immunity
  • Tumor vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

MUC1-specific anti-tumor responses : Molecular requirements for CD4-mediated responses. / VanLith, Michelle L.; Kohlgraf, Karl G.; Sivinski, Connie L.; Tempero, Richard M; Hollingsworth, Michael A.

In: International Immunology, Vol. 14, No. 8, 29.08.2002, p. 873-882.

Research output: Contribution to journalArticle

VanLith, Michelle L. ; Kohlgraf, Karl G. ; Sivinski, Connie L. ; Tempero, Richard M ; Hollingsworth, Michael A. / MUC1-specific anti-tumor responses : Molecular requirements for CD4-mediated responses. In: International Immunology. 2002 ; Vol. 14, No. 8. pp. 873-882.
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