Front Cell Dev Biol
Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, United States.
Published: January 2023
In the setting of chronic antigen exposure in the tumor microenvironment (TME), cytotoxic CD8 T cells (CTLs) lose their immune surveillance capabilities and ability to clear tumor cells as a result of their differentiation into terminally exhausted CD8 T cells. Immune checkpoint blockade (ICB) therapies reinvigorate exhausted CD8 T cells by targeting specific inhibitory receptors, thus promoting their cytolytic activity towards tumor cells. Despite exciting results with ICB therapies, many patients with solid tumors still fail to respond to such therapies and patients who initially respond can develop resistance. Recently, through new sequencing technologies such as the assay for transposase-accessible chromatin with sequencing (ATAC-seq), epigenetics has been appreciated as a contributing factor that enforces T cell differentiation toward exhaustion in the TME. Importantly, specific epigenetic alterations and epigenetic factors have been found to control CD8 T cell exhaustion phenotypes. In this review, we will explain the background of T cell differentiation and various exhaustion states and discuss how epigenetics play an important role in these processes. Then we will outline specific epigenetic changes and certain epigenetic and transcription factors that are known to contribute to CD8 T cell exhaustion. We will also discuss the most recent methodologies that are used to study and discover such epigenetic modulations. Finally, we will explain how epigenetic reprogramming is a promising approach that might facilitate the development of novel exhausted T cell-targeting immunotherapies.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846628 | PMC |
http://dx.doi.org/10.3389/fcell.2022.1082195 | DOI Listing |
Sci Immunol
January 2025
Koch Institute at MIT, Cambridge, MA 02139, USA.
Immune responses against cancer are dominated by T cell exhaustion and dysfunction. Recent advances have underscored the critical role of early priming interactions in establishing T cell fates. In this review, we explore the importance of dendritic cell (DC) signals in specifying CD8 T cell fates in cancer, drawing on insights from acute and chronic viral infection models.
View Article and Find Full Text PDFPeerJ
January 2025
Department of Emergency Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Background: Acute lung injury (ALI) is a disordered pulmonary disease characterized by acute respiratory insufficiency with tachypnea, cyanosis refractory to oxygen and diffuse alveolar infiltrates. Despite increased research into ALI, current clinical treatments lack effectiveness. Tetramethylpyrazine (TMP) has shown potential in ALI treatment, and understanding its effects on the pulmonary microenvironment and its underlying mechanisms is imperative.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
While biomarkers have been shown to enhance the prognosis of patients with colorectal cancer (CRC) compared to conventional treatments, there is a pressing need to discover novel biomarkers that can assist in assessing the prognostic impact of immunotherapy and in formulating individualized treatment plans. The RUNX family, consisting of RUNX1, RUNX2, and RUNX3, has been recognized as crucial regulators in developmental processes, with dysregulation of these genes also being implicated in tumorigenesis and cancer progression. In our present study, we demonstrated a crucial regulatory role of RUNX in CD8T and CD103CD8T cell-mediated anti-tumor response within the tumor microenvironment (TME) of human CRC.
View Article and Find Full Text PDFJ Med Virol
January 2025
Research Center, King Fahad Medical City, Riyadh Second Health Cluster, Riyadh, Saudi Arabia.
MERS is a respiratory disease caused by MERS-CoV. Multiple outbreaks have been reported, and the virus co-circulates with SARS-CoV-2. The long-term (> 6 years) cellular and humoral immune responses to MERS-CoV and their potential cross-reactivity to SARS-CoV-2 and its variants are unknown.
View Article and Find Full Text PDFJ Neuroimmune Pharmacol
January 2025
Institute of Cerebrovascular Disease Research, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.
IL-2/IL-2R inhibition improved the prognosis of ischemic stroke by regulating T cells, while the respective contribution of T cells with high/medium/low-affinity IL-2 receptors remained unclear. Single-cell RNA sequencing data of ischemic brain tissue revealed that most of the high-affinity IL-2R would be expressed by CD8 + T cells, especially by a highly-proliferative subset. Interestingly, only the CD8 + T cells with high-affinity IL-2R infiltrated ischemic brain tissues, highly expressing 32 genes (including Cdc20, Cdca3/5, and Asns) and activating 7 signaling pathways (including the interferon-alpha response pathway, a key mediator in the proliferation, migration, and cytotoxicity of CD8 + T cells).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!
© LitMetric 2025. All rights reserved.