Intratumoral T-cell infiltrates and MHC class I expression in patients with stage IV melanoma

Cancer Res. 2005 May 1;65(9):3937-41. doi: 10.1158/0008-5472.CAN-04-4621.

Abstract

The infiltration of tumors by T cells has been shown to correlate with prolonged patients' survival. However, it remains unclear why only some tumors are infiltrated with T cells. This study was designed to investigate possible correlations between intratumoral T-cell infiltrates and the expression of cancer-associated antigens and MHC class I and II molecules in patients with melanoma. Fresh frozen samples from 124 stage IV melanoma patients were analyzed by immunohistochemistry for the expression of Melan-A/MART-1, tyrosinase, gp100, NY-ESO-1, and MHC class I and II. Intratumoral T-cell and B-cell infiltrates were detected by staining with anti-CD4, anti-CD8, anti-CD3, and L26 antibodies. The NY-ESO-1 serum antibody status was assessed by Western blot analysis. Intratumoral CD8+ and CD4+ T cells were detected in 63.9% and 71.3% of patients, respectively. We observed a significant heterogeneity of the expression of the melanocyte differentiation antigens, NY-ESO-1, and MHC class I and II molecules. The only significant correlation was found between the expression of MHC class I and the presence of CD4+ and CD8+ T cells (P < 0.0001). There was a strong association between these two variables with respect to the density and distribution of infiltrating T cells and the pattern of MHC class I expression (focal versus homogenous). Intratumoral T-cell infiltration is closely correlated with the MHC class I expression but not with the expression of differentiation antigens, cancer-associated antigens, or MHC class II molecules. These results may have implications for the definition of prognostic variables and for the identification of patients who may benefit from antigen-specific cancer immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neoplasm / immunology
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • MART-1 Antigen
  • Melanoma / immunology*
  • Melanoma / pathology
  • Membrane Glycoproteins / immunology
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / immunology
  • Monophenol Monooxygenase / immunology
  • Neoplasm Proteins / immunology
  • Neoplasm Staging
  • gp100 Melanoma Antigen

Substances

  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Histocompatibility Antigens Class I
  • MART-1 Antigen
  • MLANA protein, human
  • Membrane Glycoproteins
  • Membrane Proteins
  • Neoplasm Proteins
  • PMEL protein, human
  • gp100 Melanoma Antigen
  • Monophenol Monooxygenase