Cytokine-Induced Senescence in the Tumor Microenvironment and Its Effects on Anti-Tumor Immune Responses
Abstract
:Simple Summary
Abstract
1. Introduction
2. The Tumor Microenvironment (TME)
2.1. Tumor Cells
2.2. Immune Cells in the TME
2.2.1. Tumor-Infiltrating Lymphocytes (TILs)
2.2.2. Myeloid Cells
2.3. Stromal Cells in the TME
2.4. The Extracellular Matrix (ECM)
3. Immune Surveillance of Tumors by Toxic and Non-Toxic Mechanisms
4. Senescence Induction in the TME
4.1. Cytokine-Induced Senescence (CIS)
4.2. Senescence Induction in Cells of the Immune System
5. Immunosurveillance of Senescent Cells
6. Conclusions and Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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Cell Type | Inducer(s) | Response (Mechanism of Growth Arrest) | Refs. |
---|---|---|---|
Human umbilical vein endothelial cells (HUVECs) | IFN-γ | Induction of senescence (via oxidative stress & DNA damage) | [115] |
Murine intrahepatic biliary epithelial cells (mBECs) | IFN-β/IFN-γ/TNF | Induction of senescence (via oxidative stress & ATM/p53 pathway) | [112] |
Murine pancreatic β-cell tumors, murine and human cancer cell lines, primary human cancer cells | Th1 cells/IFN-γ + TNF | Induction of senescence (via p16/Rb pathway) | [25] |
Human primary melanocytes | IFN-γ | Induction of senescence & apoptosis (via oxidative stress & p21 upregulation) | [116] |
Human rhabdomyosarcoma (cell lines and primary cancer cells) | Tumor-targeted IL-12 (via secretion of IFN-γ + TNF) | Induction of senescence & differentiation (via p16 or p21 upregulation) | [107] |
Human peritoneal carcinomatosis of colorectal cancer | Immune cell interactions in the TME (via secretion of IFN-γ + TNF) | Induction of senescence (via p21 upregulation) | [110] |
Human cancer cell lines (breast and cervix), primary human fibroblasts | IFN-γ | Induction of senescence (via oxidative stress, DNA damage, and TGF-β/SMAD signaling) | [117] |
Human umbilical vein endothelial cells (HUVECs) | TNF | Induction of senescence (via oxidative stress, DNA damage, and JAK/STAT signaling) | [122] |
Human breast cancer cell lines | Th1 cells/IFN-γ + TNF (also combined with different antibodies) | Induction of senescence & apoptosis (via p15 & p16 upregulation) | [121] |
Murine melanoma cell line | IFN-γ + TNF | Induction of reversible senescence (via p21 upregulation) | [119] |
Murine B cell lymphoma, murine pancreatic β-cell tumors | Immune checkpoint blockade therapy (also combined with adoptive Th1 cell transfer [26]) | Induction of senescence (via p16 or p21 upregulation) | [26,126] |
Human cancer cell lines (bladder, melanoma, and breast) | IL-2/IL-12/IL-18-stimulated γδ T cells (via secretion of IFN-γ + TNF) | Induction of senescence (via p21 upregulation) | [109] |
Human melanoma cell lines | Co-culture-derived supernatants from non- classical monocytes (slanMo) and NK cells (via secretion of IFN-γ + TNF) | Induction of senescence (via p21 upregulation) | [120] |
Murine aortic endothelial cells (MAECs) | Th17 cells/IL-17A | Induction of senescence (via NF-κB/p53/Rb pathway) | [124] |
Human breast cancer cell line | IL-32θ | Induction of senescence (mechanism unclear) | [125] |
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Rentschler, M.; Braumüller, H.; Briquez, P.S.; Wieder, T. Cytokine-Induced Senescence in the Tumor Microenvironment and Its Effects on Anti-Tumor Immune Responses. Cancers 2022, 14, 1364. https://doi.org/10.3390/cancers14061364
Rentschler M, Braumüller H, Briquez PS, Wieder T. Cytokine-Induced Senescence in the Tumor Microenvironment and Its Effects on Anti-Tumor Immune Responses. Cancers. 2022; 14(6):1364. https://doi.org/10.3390/cancers14061364
Chicago/Turabian StyleRentschler, Maximilian, Heidi Braumüller, Priscilla S. Briquez, and Thomas Wieder. 2022. "Cytokine-Induced Senescence in the Tumor Microenvironment and Its Effects on Anti-Tumor Immune Responses" Cancers 14, no. 6: 1364. https://doi.org/10.3390/cancers14061364