Direct T cell-tumour interaction triggers T H 1 phenotype activation through the modification of the mesenchymal stromal cells transcriptional programme

P. Jin, S. Civini, Y. Zhao, V. De Giorgi, J. Ren, M. Sabatino, J. Jin, H. Wang, Davide Bedognetti, F. Marincola, D. Stroncek

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 T H 1 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 T H 1 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 T H 1 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.

Original languageEnglish
Pages (from-to)2955-2964
Number of pages10
JournalBritish Journal of Cancer
Volume110
Issue number12
DOIs
Publication statusPublished - 10 Jun 2014
Externally publishedYes

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Mesenchymal Stromal Cells
Cell Communication
T-Lymphocytes
Phenotype
Tumor-Infiltrating Lymphocytes
Neoplasms
Cytokines
Melanoma
Indoleamine-Pyrrole 2,3,-Dioxygenase
Melanoma-Specific Antigens
Tumor Microenvironment
Interleukin-12
Immunosuppressive Agents
Transcriptome
Wound Healing
Clone Cells
Antigens
Growth

Keywords

  • MSC
  • TH1 phenotype
  • Tumour microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Direct T cell-tumour interaction triggers T H 1 phenotype activation through the modification of the mesenchymal stromal cells transcriptional programme. / Jin, P.; Civini, S.; Zhao, Y.; De Giorgi, V.; Ren, J.; Sabatino, M.; Jin, J.; Wang, H.; Bedognetti, Davide; Marincola, F.; Stroncek, D.

In: British Journal of Cancer, Vol. 110, No. 12, 10.06.2014, p. 2955-2964.

Research output: Contribution to journalArticle

Jin, P, Civini, S, Zhao, Y, De Giorgi, V, Ren, J, Sabatino, M, Jin, J, Wang, H, Bedognetti, D, Marincola, F & Stroncek, D 2014, 'Direct T cell-tumour interaction triggers T H 1 phenotype activation through the modification of the mesenchymal stromal cells transcriptional programme', British Journal of Cancer, vol. 110, no. 12, pp. 2955-2964. https://doi.org/10.1038/bjc.2014.235
Jin, P. ; Civini, S. ; Zhao, Y. ; De Giorgi, V. ; Ren, J. ; Sabatino, M. ; Jin, J. ; Wang, H. ; Bedognetti, Davide ; Marincola, F. ; Stroncek, D. / Direct T cell-tumour interaction triggers T H 1 phenotype activation through the modification of the mesenchymal stromal cells transcriptional programme. In: British Journal of Cancer. 2014 ; Vol. 110, No. 12. pp. 2955-2964.
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AU - Zhao, Y.

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AU - Ren, J.

AU - Sabatino, M.

AU - Jin, J.

AU - Wang, H.

AU - Bedognetti, Davide

AU - Marincola, F.

AU - Stroncek, D.

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N2 - 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 T H 1 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 T H 1 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 T H 1 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.

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