Targeting STAT3 and STAT5 in Tumor-Associated Immune Cells to Improve Immunotherapy
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/12/1832 |
| _version_ | 1797706484489912320 |
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| author | Grégory Verdeil Toby Lawrence Anne-Marie Schmitt-Verhulst Nathalie Auphan-Anezin |
| author_facet | Grégory Verdeil Toby Lawrence Anne-Marie Schmitt-Verhulst Nathalie Auphan-Anezin |
| author_sort | Grégory Verdeil |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T05:51:56Z |
| format | Article |
| id | doaj.art-dce2bb3abd84451f8a44857a64f9c76a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T05:51:56Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-dce2bb3abd84451f8a44857a64f9c76a2023-09-03T05:03:52ZengMDPI AGCancers2072-66942019-11-011112183210.3390/cancers11121832cancers11121832Targeting STAT3 and STAT5 in Tumor-Associated Immune Cells to Improve ImmunotherapyGrégory Verdeil0Toby Lawrence1Anne-Marie Schmitt-Verhulst2Nathalie Auphan-Anezin3Laboratory Regulation of Immune Dysfunction in Cancer, Department of Oncology, University of Lausanne, CH-1066 Epalinges, SwitzerlandAix 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, FranceAix 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, FranceAix 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, FranceOncogene-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.https://www.mdpi.com/2072-6694/11/12/1832inflammationtumor-associated macrophagesadoptive t cell therapyimmune suppressionstat transcription factors |
| spellingShingle | Grégory Verdeil Toby Lawrence Anne-Marie Schmitt-Verhulst Nathalie Auphan-Anezin Targeting STAT3 and STAT5 in Tumor-Associated Immune Cells to Improve Immunotherapy Cancers inflammation tumor-associated macrophages adoptive t cell therapy immune suppression stat transcription factors |
| title | Targeting STAT3 and STAT5 in Tumor-Associated Immune Cells to Improve Immunotherapy |
| title_full | Targeting STAT3 and STAT5 in Tumor-Associated Immune Cells to Improve Immunotherapy |
| title_fullStr | Targeting STAT3 and STAT5 in Tumor-Associated Immune Cells to Improve Immunotherapy |
| title_full_unstemmed | Targeting STAT3 and STAT5 in Tumor-Associated Immune Cells to Improve Immunotherapy |
| title_short | Targeting STAT3 and STAT5 in Tumor-Associated Immune Cells to Improve Immunotherapy |
| title_sort | targeting stat3 and stat5 in tumor associated immune cells to improve immunotherapy |
| topic | inflammation tumor-associated macrophages adoptive t cell therapy immune suppression stat transcription factors |
| url | https://www.mdpi.com/2072-6694/11/12/1832 |
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