title: Pancreatic cancer alters human CD4+ T lymphocyte function: a piece in the immune evasion puzzle.
abstract: OBJECTIVE
  To verify whether the dysregulation of CD4 T cells concurs in worsening the outcome of pancreatic cancer, we compared the effects of pancreatic cancer and other gastrointestinal cancer cell-conditioned media on the (1) proliferation, migration, and differentiation of CD4 T cells and (2) expansion of CD4 memory (CD45RO), naive (CD45RA), activated (CD69), and regulatory (CD25) subsets.
  
  
  METHODS
  After culture of CD4 T cells in control, pancreatic (BxPC3, Capan1, MiaPaCa2), or gastrointestinal cancer (AGS, HepG2, HT29) cell-conditioned media, we evaluated proliferation, migration, interferon γ (IFNγ) production, and CD45RA, CD45RO, CD69, and CD25 membrane expression in control and conditioned CD4 T cells.
  
  
  RESULTS
  Only pancreatic cancer-conditioned media (1) inhibited CD4 T-cell proliferation (P < 0.001) and migration under human stromal cell-derived factor-α chemotaxis (P < 0.001) and (2) induced CD4 T-cell IFNγ production (P < 0.05) and the expansion of the CD69-positive subset (P < 0.001) with respect to the control, with no changes being found in the CD45RA, CD45RO, and CD25 subsets.
  
  
  CONCLUSIONS
  The in vitro findings achieved in the present study demonstrate that pancreatic cancer cells inhibit CD4 T-cell proliferation and migration, induce IFNγ production, and favor a CD69 subset expansion, suggesting that CD4 T cells play an important role in pancreatic cancer immune evasion.
authors.affiliation: Department of Laboratory Medicine, University of Padova, Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Fogar
authors.forename: Daniela
authors.initials: D
authors.lastname: Basso
authors.forename: Elisa
authors.initials: E
authors.lastname: Fadi
authors.forename: Eliana
authors.initials: E
authors.lastname: Greco
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pantano
authors.forename: Andrea
authors.initials: A
authors.lastname: Padoan
authors.forename: Dania
authors.initials: D
authors.lastname: Bozzato
authors.forename: Monica
authors.initials: M
authors.lastname: Facco
authors.forename: Maria Colomba
authors.initials: MC
authors.lastname: Sanzari
authors.forename: Sara
authors.initials: S
authors.lastname: Teolato
authors.forename: Carlo-Federico
authors.initials: CF
authors.lastname: Zambon
authors.forename: Filippo
authors.initials: F
authors.lastname: Navaglia
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Semenzato
authors.forename: Sergio
authors.initials: S
authors.lastname: Pedrazzoli
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D017077:Culture Media, Conditioned / Q000378:metabolism; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D019139:Tumor Escape; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017077:Culture Media, Conditioned; D007371:Interferon-gamma; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D000099192:CD69 Antigens; C508017:IL2RA protein, human; C516769:PTPRC protein, human