Cancer cell immune evasion: epigenetic mechanisms and emerging therapeutic strategies

Despite significant advances in cancer immunotherapy, many patients fail to respond or eventually relapse due to immune evasion and therapeutic resistance. A major mechanism underlying this resistance is epigenetic reprogramming within the tumor microenvironment (TME). Tumors exploit DNA methylation, histone modifications, and chromatin remodeling to suppress antigen presentation, silence immune-stimulatory pathways, and establish an immunosuppressive niche enriched with myeloid-derived suppressor cells (MDSCs) and exhausted T-cells. These alterations contribute to poor T-cell infiltration and resistance to immune checkpoint blockade, particularly in epigenetically “cold” tumors.Recent studies have revealed how transcriptional repressors, chromatin-modifying enzymes, and noncoding RNAs orchestrate immune escape and tumor progression. In parallel, targeted protein degradation technologies, particularly PROTACs (Proteolysis-Targeting Chimeras), have emerged as promising tools to selectively eliminate epigenetic and immune-regulatory proteins that drive immune suppression.This Research Topic aims to bring together interdisciplinary research focused on epigenetic immune evasion, targeted protein degradation strategies, biomarker discovery, and innovative therapeutic approaches to overcome resistance and advance precision cancer immunotherapy.This Research Topic seeks to address the urgent challenge of immune evasion in cancer, with a focus on the epigenetic mechanisms that enable tumors to escape immune recognition and resist immunotherapy. Epigenetic dysregulation within the tumor microenvironment plays a key role in shaping immune suppression by altering gene expression, silencing tumor antigens, and reprogramming both T-cells and myeloid cells toward dysfunctional states. To tackle these challenges, we must deepen our understanding of the molecular drivers of epigenetic immune escape and translate this knowledge into effective therapeutic strategies and early detection tools. Recent advances, such as single-cell epigenomics, liquid biopsy-based biomarker discovery, and spatial mapping of immune-epigenetic interactions are opening new frontiers in monitoring and predicting immune resistance.Importantly, emerging therapeutic platforms such as PROTACs, which enable targeted degradation of epigenetic regulators and immune-modulatory proteins, are providing promising strategies to reverse immune evasion and enhance antitumor immunity. By bringing together contributions from basic, translational, and clinical researchers, this Topic aims to drive innovation at the intersection of epigenetics, immunology, and therapeutic engineering.This Research Topic invites contributions exploring the role of epigenetic regulation in cancer immune evasion, as well as the development of novel therapeutic strategies and biomarker platforms to combat immunotherapy resistance. We welcome interdisciplinary work that bridges cancer biology, immunology, and therapeutic innovation.Key themes include:• Epigenetic mechanisms of immune suppression and T-cell dysfunction• Chromatin remodeling, DNA methylation, and noncoding RNAs in immune escape• Myeloid cell reprogramming via epigenetic pathways• Identification of predictive epigenetic biomarkers for immune resistance• Application of PROTACs to target epigenetic and immune regulators• Integration of single-cell and spatial epigenomics in tumor-immune profiling• Combination therapies: epigenetic drugs with immunotherapeutics• Immune evasion mechanisms and therapeutic strategies in the inflammation-to-cancer transition of the digestive systemWe welcome the following manuscript types:• Original Research• Reviews and Mini-Reviews• Perspectives and Opinions• Methods and Technology Papers• Translational or Clinical Case StudiesThis Topic aims to advance our understanding of immune-epigenetic interplay and drive therapeutic innovation in oncology.Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic. Topic editors: Kishu Ranjan, Fer. Aranda Vega Source: https://www.frontiersin.org/research-topics/81268/cancer-cell-immune-evasion-epigenetic-mechanisms-and-emerging-therapeutic-strategies