title: The immunophenotype and activation status of the lymphocytic infiltrate in human breast cancers, the role of the major histocompatibility complex in cell-mediated immune mechanisms, and their association with prognostic indicators.
abstract: BACKGROUND
  The aims of this study were to characterize, phenotypically, the immune infiltrate in human breast cancers, to assess the activation status of tumor-infiltrating lymphocytes (TIL), and to define the association of these findings with established prognostic indicators.
  
  
  METHODS
  Immunohistochemistry was performed on frozen sections of 60 primary breast cancers by use of monoclonal antibodies to T lymphocytes (CD3), T-helper cells (CD4), cytotoxic T-cells (CD8), natural killer cells (CD56), interleukin-2 receptors (IL-2R), and major histocompatibility (MHC) class I antigen (HLA-ABC) and MHC class II antigen (HLA-DR).
  
  
  RESULTS
  All tumors stained positive for CD3, CD4 and CD8, but with marked variation in the intensity of the infiltrate. In tumors with a moderate infiltrate of TIL, there was a trend toward a greater representation of T-helper cells. However, as the intensity of TIL increased, there was a decline in the proportion of T-helper cells and a concomitant rise in the relative proportion of cytotoxic T cells. There was a relative paucity of natural killer cells. A significant association was found between the intensity of TIL and the number of positive nodes (P=.02) and the intensity of the infiltrate of both T-helper cells and cytotoxic T cells with ER expression (P=.03 and.05, respectively). Most tumors stained positive for IL-2R. The expression of IL-2R was associated with the intensity of TIL (P<.0001), T-helper cells (P<.002), cytotoxic T cells (P=.01) and natural killer cells (P=0.04), and also with the degree of lymph node positivity (P=.02) and histologic tumor grade (P=.05). MHC class II expression was variable, and a large proportion of the tumors showed limited expression in individual cancer cells. There was an association between the expression of HLA-DR in tumor cells and the activation status of TIL (P=.03).
  
  
  CONCLUSIONS
  An immune infiltrate is an invariable finding in breast cancers, and the intensity of the infiltrate is greater in node positive tumors. Additionally, TIL may well be activated, albeit partially, in most tumors, suggesting that cell-mediated immune mechanisms are functionally intact.
authors.affiliation: Department of Academic Surgery, Barts and the London NHS Trust, The Royal London Hospital, Whitechapel, London E1 1BB, United Kingdom.
authors.forename: Stavros N
authors.initials: SN
authors.lastname: Georgiannos
authors.forename: Andrew
authors.initials: A
authors.lastname: Renaut
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Goode
authors.forename: Michael
authors.initials: M
authors.lastname: Sheaff
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D011379:Prognosis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D015375:Receptors, Interleukin-2