Cancer immunotherapy with immune checkpoint therapy and adoptive T cell therapy has provided durable clinical benefits to patients. However, only a subset of patients treated with immunotherapy respond, and the response rates vary across different tumor types. Response or resistance to immunotherapy largely depends on the functional states and spatial distribution of T lymphocytes and myeloid cells in the tumor microenvironment. Recent advances demonstrated that epigenetic modifications and metabolic reprogramming of both tumor and stromal cells critically shape antitumor immunity. Thus, and given the intimate role of these biological pathways in cancer maintenance, progression, and resistance to targeted therapies and immunotherapies, their validation in pre-clinical and translational studies is essential in developing rational therapeutic strategies that will extend the durable clinical benefit of immunotherapy to a broader patient population.
Epigenetic machinery dynamically coordinates gene expression through a variety of mechanisms that include DNA methylation, histone post-translational modifications, promoter-enhancer interactions, and chromatin remodeling complexes. This process determines the cell type–specific gene expression characteristics of specific cellular phenotypes. Although significant progress in understanding the role of the epigenetic machinery in cancer initiation and progression has been made, the epigenetic symbiosis between tumor, immune and other stromal cells and its impacts on sensitivity to immunotherapy are not well understood. Further, emerging evidences suggest that metabolic pathways in the tumor immune microenvironment orchestrates epigenetic and immune reprograming, highlighting the importance to of the metabolic-epigenetic-immunity axis in the outcome of immunotherapy.
The aim of this Research Topic is to highlight original research and review articles focusing on epigenetic and metabolic pathways regulating primary and adaptive resistance to ICT. We welcome the submission of Original Research Articles, Reviews, and Mini Reviews, which cover, but are not limited to, the following topics
• Studies outlining the role of epigenetic pathways and regulation of epigenetic mechanisms in the tumor-immune ecosystem that may determine the durability of tumor responses to immunotherapy;
• Identification of key regulators of metabolic pathways with an impact on cellular plasticity in the elaborate tumor microenvironment and anti-tumor immunity.
• Technical advances in understanding the epigenetic and metabolic pathways in pre-clinical and clinical studies.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Dr. Apostolou is employed by Sumitomo Dainippon Pharma Oncology. The other Topic Editors declare no competing interests with regards to the Research Topic
Cancer immunotherapy with immune checkpoint therapy and adoptive T cell therapy has provided durable clinical benefits to patients. However, only a subset of patients treated with immunotherapy respond, and the response rates vary across different tumor types. Response or resistance to immunotherapy largely depends on the functional states and spatial distribution of T lymphocytes and myeloid cells in the tumor microenvironment. Recent advances demonstrated that epigenetic modifications and metabolic reprogramming of both tumor and stromal cells critically shape antitumor immunity. Thus, and given the intimate role of these biological pathways in cancer maintenance, progression, and resistance to targeted therapies and immunotherapies, their validation in pre-clinical and translational studies is essential in developing rational therapeutic strategies that will extend the durable clinical benefit of immunotherapy to a broader patient population.
Epigenetic machinery dynamically coordinates gene expression through a variety of mechanisms that include DNA methylation, histone post-translational modifications, promoter-enhancer interactions, and chromatin remodeling complexes. This process determines the cell type–specific gene expression characteristics of specific cellular phenotypes. Although significant progress in understanding the role of the epigenetic machinery in cancer initiation and progression has been made, the epigenetic symbiosis between tumor, immune and other stromal cells and its impacts on sensitivity to immunotherapy are not well understood. Further, emerging evidences suggest that metabolic pathways in the tumor immune microenvironment orchestrates epigenetic and immune reprograming, highlighting the importance to of the metabolic-epigenetic-immunity axis in the outcome of immunotherapy.
The aim of this Research Topic is to highlight original research and review articles focusing on epigenetic and metabolic pathways regulating primary and adaptive resistance to ICT. We welcome the submission of Original Research Articles, Reviews, and Mini Reviews, which cover, but are not limited to, the following topics
• Studies outlining the role of epigenetic pathways and regulation of epigenetic mechanisms in the tumor-immune ecosystem that may determine the durability of tumor responses to immunotherapy;
• Identification of key regulators of metabolic pathways with an impact on cellular plasticity in the elaborate tumor microenvironment and anti-tumor immunity.
• Technical advances in understanding the epigenetic and metabolic pathways in pre-clinical and clinical studies.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Dr. Apostolou is employed by Sumitomo Dainippon Pharma Oncology. The other Topic Editors declare no competing interests with regards to the Research Topic