Molecular Mechanisms of Resistance to Immunotherapy and Antiangiogenic Treatments in Clear Cell Renal Cell Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Molecular Pathways Associated with Resistance to Treatment with Tyrosine-Kinase Inhibitors
2.1. Hypoxia as a Resistance Inductor
2.2. Angiogenic Switch
2.3. Epithelial–Mesenchymal Transition (EMT)
2.4. Activating Bypass Pathways
2.4.1. VEGF
2.4.2. PTEN
2.4.3. FGF
2.4.4. Axl and c-MET
2.4.5. TNF-α
2.4.6. Angiopoietin/Tie Pathway
2.4.7. Enhancer of Zeste Homologue 2 (EZH2)
2.5. Lysosomal Sequestration of TKIs
2.6. Noncoding RNAs (ncRNA) and Single Nucleotide Polymorphisms
2.7. Tumor Microenvironment Factors Related to Resistance to TKIs
2.7.1. Tumor Endothelial Cells (TECs)
2.7.2. Bone Marrow-Derived Proangiogenic Inflammatory Cell Recruitment
2.7.3. Pericyte Coverage
2.7.4. Tumor-Associated Fibroblasts (TAFs)
2.7.5. Tumor-Associated Macrophages
3. Molecular Pathways Associated with Resistance to Treatment with Immune Checkpoint Inhibitors
3.1. Tumor Cells-Intrinsic Factors
3.1.1. Interferon Gamma Signaling Pathway
3.1.2. Wnt/β-catenin Pathway
3.1.3. Mitogen-Activated Protein Kinases (MAPK) Pathway
3.1.4. PI3K/AKT/m-TOR Pathway
3.1.5. Cell Cycle Checkpoint Pathway
3.1.6. Loss of MHC
3.2. Tumor Microenvironment Related Factors and their Role in Resistance to Immune Response
3.2.1. T Cells
3.2.2. Innate Immune System
3.2.3. B Cells and Tertiary Lymphoid Structures
3.2.4. Proinflammatory Cytokines
3.2.5. Hypoxia
3.2.6. Protein Polybromo-1(PBRM-1) Expression
3.2.7. Immune Escape Related to Other Immune Checkpoints
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Ballesteros, P.Á.; Chamorro, J.; Román-Gil, M.S.; Pozas, J.; Gómez Dos Santos, V.; Granados, Á.R.; Grande, E.; Alonso-Gordoa, T.; Molina-Cerrillo, J. Molecular Mechanisms of Resistance to Immunotherapy and Antiangiogenic Treatments in Clear Cell Renal Cell Carcinoma. Cancers 2021, 13, 5981. https://doi.org/10.3390/cancers13235981
Ballesteros PÁ, Chamorro J, Román-Gil MS, Pozas J, Gómez Dos Santos V, Granados ÁR, Grande E, Alonso-Gordoa T, Molina-Cerrillo J. Molecular Mechanisms of Resistance to Immunotherapy and Antiangiogenic Treatments in Clear Cell Renal Cell Carcinoma. Cancers. 2021; 13(23):5981. https://doi.org/10.3390/cancers13235981
Chicago/Turabian StyleBallesteros, Pablo Álvarez, Jesús Chamorro, María San Román-Gil, Javier Pozas, Victoria Gómez Dos Santos, Álvaro Ruiz Granados, Enrique Grande, Teresa Alonso-Gordoa, and Javier Molina-Cerrillo. 2021. "Molecular Mechanisms of Resistance to Immunotherapy and Antiangiogenic Treatments in Clear Cell Renal Cell Carcinoma" Cancers 13, no. 23: 5981. https://doi.org/10.3390/cancers13235981