title: Intratumoral T-cell infiltrates and MHC class I expression in patients with stage IV melanoma.
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.
authors.affiliation: II. Medizinische Klinik-Onkologie, Krankenhaus Nordwest, Frankfurt, Germany. albatran@aol.com
authors.forename: Salah-Eddin
authors.initials: SE
authors.lastname: Al-Batran
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Rafiyan
authors.forename: Akin
authors.initials: A
authors.lastname: Atmaca
authors.forename: Antje
authors.initials: A
authors.lastname: Neumann
authors.forename: Julia
authors.initials: J
authors.lastname: Karbach
authors.forename: Armin
authors.initials: A
authors.lastname: Bender
authors.forename: Eckhart
authors.initials: E
authors.lastname: Weidmann
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Altmannsberger
authors.forename: Alexander
authors.initials: A
authors.lastname: Knuth
authors.forename: Elke
authors.initials: E
authors.lastname: Jäger
mesh_terms: D000912:Antibodies, Neoplasm / Q000276:immunology; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology; D014442:Monophenol Monooxygenase / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D009367:Neoplasm Staging; D058951:gp100 Melanoma Antigen
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D015395:Histocompatibility Antigens Class I; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase