Tumor antigens and antigen-presenting capacity in breast cancer

Pathobiology. 2002-2003;70(6):324-32. doi: 10.1159/000071272.

Abstract

Aims: Cancer cells frequently express antigens capable of being recognized by the host immune system; however, any resultant immune response is often ineffective. This may be related in part to tumor-induced defects in antigen presentation. We screened for dendritic cell infiltration, tumor MHC II expression and associated lymphocytic reaction in the context of three established breast tumor antigens.

Methods: Forty primary breast tumors were evaluated by immunohistochemical techniques for expression of her2/neu, p53, and MUC1 and MHC class II molecules. Twenty-five samples were further analyzed for p53 mutations by PCR-SSCP analysis and DNA sequencing. The phenotype of tumor-infiltrating inflammatory cells was evaluated using the following markers: CD1a, MHC Class II, CD3, CD45, and CD45RO.

Results: Tumors with p53 mutations and overexpression, but not her2/neu or MUC1 overexpressing tumors, more frequently harbored marked CD1a+ dendritic cell infiltrates. An overall correlation between CD1a+ cell infiltrates and HLA class II expression on tumor cells (p = 0.0008) was also observed and these tumors had greater CD45RO+ lymphocytic infiltrates.

Conclusions: In breast cancer, p53 mutations may present a more visible signal to the immune system and hence provide a better target for immunotherapy. Infiltrating CD1a positive cells are associated with a more dense tumor lymphocytic infiltrate and tumor cell expression of MHC II molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigen Presentation / immunology*
  • Antigens, CD1 / metabolism
  • Antigens, Neoplasm*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • DNA Mutational Analysis
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Middle Aged
  • Mucin-1 / metabolism
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Receptor, ErbB-2 / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antigens, CD1
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CD1a antigen
  • Histocompatibility Antigens Class II
  • Mucin-1
  • Tumor Suppressor Protein p53
  • Receptor, ErbB-2