title: Different subsets of tumor-infiltrating lymphocytes correlate with macrophage influx and monosomy 3 in uveal melanoma.
abstract: OBJECTIVE
  In contrast to many other malignancies, in uveal melanoma (UM) the presence of an immune infiltrate is associated with a bad prognosis. An analysis of the different functional phenotypes of tumor-infiltrating leukocytes (TIL) and a comparison with the genetic background of the tumors may help to explain this apparent anomaly.
  
  
  METHODS
  We performed a comprehensive immunohistochemical study by evaluating the density of CD8(+) and CD4(+) T lymphocytes, forkhead box p3 (Foxp3(+)) regulatory T cells (Tregs), and CD68(+) and CD68(+)CD163(+) macrophages in 43 cases of UM in relation to tumor characteristics. Expression of the chemokines CCL2, CCL17, and CCL22 in cultured human UM cells and peripheral blood monocytes was analyzed by quantitative PCR (qPCR).
  
  
  RESULTS
  The presence of TILs was highly variable between tumors and was dominated by CD8(+) T cells with fewer CD4(+) T cells and Tregs. When tumors were infiltrated by immune cells, the infiltrate generally comprised all different subsets of lymphocytes (P < 0.001) and M2 macrophages (P < 0.001). Different T-cell ratios did not influence clinical outcome. In addition, the presence of TIL correlated with the loss of one chromosome 3 (P < 0.04). UM cells express CCL2 and CCL22, two chemokines known to mediate trafficking of immune cells to the tumor.
  
  
  CONCLUSIONS
  All studied subtypes of tumor-infiltrating immune cells were collectively increased and showed an association with monosomy of chromosome 3 suggesting that tumor intrinsic factors control the leukocyte influx, possibly through local chemokine secretion.
authors: Departments of Ophthalmology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors: Inge H G
authors: IH
authors: Bronkhorst
authors: T H Khanh
authors: TH
authors: Vu
authors: Ekaterina S
authors: ES
authors: Jordanova
authors: Gregorius P M
authors: GP
authors: Luyten
authors: Sjoerd H van der
authors: SH
authors: Burg
authors: Martine J
authors: MJ
authors: Jager
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054422:Chemokine CCL22 / Q000378:metabolism; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016131:Lymphocyte Subsets / Q000378:metabolism*; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012044:Regression Analysis; D014604:Uveal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology*
chemical_list: D018932:Chemokine CCL2; D054422:Chemokine CCL22; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II