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Targeting STAT3 and STAT5 in Tumor-Associated Immune Cells to Improve Immunotherapy.

  • Verdeil G Laboratory Regulation of Immune Dysfunction in Cancer, Department of Oncology, University of Lausanne, CH-1066 Epalinges, Switzerland.
  • Lawrence T Aix Marseille University, Centre National de la Recherche Scientifique (CNRS) UMR7280, Institut National de la Santé et de la Recherche Médicale (INSERM) U1104, Centre Immunologie Marseille-Luminy (CIML), Parc Scientifique de Luminy, Case 906, 13288 Marseille, CEDEX 09, France.
  • Schmitt-Verhulst AM Aix Marseille University, Centre National de la Recherche Scientifique (CNRS) UMR7280, Institut National de la Santé et de la Recherche Médicale (INSERM) U1104, Centre Immunologie Marseille-Luminy (CIML), Parc Scientifique de Luminy, Case 906, 13288 Marseille, CEDEX 09, France.
  • Auphan-Anezin N Aix Marseille University, Centre National de la Recherche Scientifique (CNRS) UMR7280, Institut National de la Santé et de la Recherche Médicale (INSERM) U1104, Centre Immunologie Marseille-Luminy (CIML), Parc Scientifique de Luminy, Case 906, 13288 Marseille, CEDEX 09, France.
  • 2019-11-27
Published in:
  • Cancers. - 2019
STAT transcription factors
adoptive T cell therapy
immune suppression
inflammation
tumor-associated macrophages
English Oncogene-induced STAT3-activation is central to tumor progression by promoting cancer cell expression of pro-angiogenic and immunosuppressive factors. STAT3 is also activated in infiltrating immune cells including tumor-associated macrophages (TAM) amplifying immune suppression. Consequently, STAT3 is considered as a target for cancer therapy. However, its interplay with other STAT-family members or transcription factors such as NF-κB has to be considered in light of their concerted regulation of immune-related genes. Here, we discuss new attempts at re-educating immune suppressive tumor-associated macrophages towards a CD8 T cell supporting profile, with an emphasis on the role of STAT transcription factors on TAM functional programs. Recent clinical trials using JAK/STAT inhibitors highlighted the negative effects of these molecules on the maintenance and function of effector/memory T cells. Concerted regulation of STAT3 and STAT5 activation in CD8 T effector and memory cells has been shown to impact their tumor-specific responses including intra-tumor accumulation, long-term survival, cytotoxic activity and resistance toward tumor-derived immune suppression. Interestingly, as an escape mechanism, melanoma cells were reported to impede STAT5 nuclear translocation in both CD8 T cells and NK cells. Ours and others results will be discussed in the perspective of new developments in engineered T cell-based adoptive therapies to treat cancer patients.
Language
  • English
Open access status
gold
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https://sonar.ch/global/documents/186365
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