title: Direct T cell-tumour interaction triggers TH1 phenotype activation through the modification of the mesenchymal stromal cells transcriptional programme.
abstract: BACKGROUND
  Mesenchymal stromal cells (MSCs) are heterogeneous cells with immunoregulatory and wound-healing properties. In cancer, they are known to be an essential part of the tumour microenvironment. However, their role in tumour growth and rejection remains unclear. To investigate this, we co-cultured human MSCs, tumour infiltrating lymphocytes (TIL), and melanoma cells to investigate the role of MSCs in the tumour environment.
  
  
  METHODS
  Mesenchymal stromal cells were co-cultured with melanoma antigen-specific TIL that were stimulated either with HLA-A*0201(+) melanoma cells or with a corresponding clone that had lost HLA-A*0201 expression.
  
  
  RESULTS
  Activated TIL induced profound pro-inflammatory gene expression signature in MSCs. Analysis of culture supernatant found that MSCs secreted pro-inflammatory cytokines, including TH1 cytokines that have been previously associated with immune-mediated antitumor responses. In addition, immunohistochemical analysis on selected markers revealed that the same activated MSCs secreted both the TH1 cytokine (interleukin-12) and indoleamine 2,3 dioxygenase (IDO), a classical immunosuppressive factor.
  
  
  CONCLUSIONS
  This study reflected that the plasticity of MSCs is highly dependent upon microenvironment conditions. Tumour-activated TIL induced TH1 phenotype change in MSCs that is qualitatively similar to the previously described immunologic constant of rejection signature observed during immune-mediated, tissue-specific destruction. This response may be responsible for the in loco amplification of antigen-specific anti-cancer immune response.
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: P
authors.initials: P
authors.lastname: Jin
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: S
authors.initials: S
authors.lastname: Civini
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: V
authors.initials: V
authors.lastname: De Giorgi
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ren
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sabatino
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: J
authors.initials: J
authors.lastname: Jin
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: D
authors.initials: D
authors.lastname: Bedognetti
authors.affiliation: 1] Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA [2] Sidra Medical and Research Centre, Doha, Qatar.
authors.forename: F
authors.initials: F
authors.lastname: Marincola
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: D
authors.initials: D
authors.lastname: Stroncek
mesh_terms: D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015789:HLA-A2 Antigen / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D053765:Interleukin-12 Subunit p35 / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D016207:Cytokines; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C508858:IL12A protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053765:Interleukin-12 Subunit p35