Naïve T cells are poorly studied in cancer patients. We report that naïve T cells are prone to undergo apoptosis due to a selective loss of FAK family-interacting protein of 200 kDa (FIP200) in ovarian cancer patients and tumor-bearing mice. This results in poor antitumor immunity via autophagy deficiency, mitochondria overactivation, and high reactive oxygen species production in T cells. Mechanistically, loss of FIP200 disables the balance between proapoptotic and antiapoptotic Bcl-2 family members via enhanced argonaute 2 (Ago2) degradation, reduced Ago2 and microRNA1198-5p complex formation, less microRNA1198-5p maturation, and consequently abolished microRNA1198-5p-mediated repression on apoptotic gene Bcl-2 overexpression and mitochondria complex I inhibition rescue T cell apoptosis and promoted tumor immunity. Tumor-derived lactate translationally inhibits FIP200 expression by down-regulating the nicotinamide adenine dinucleotide level while potentially up-regulating the inhibitory effect of adenylate-uridylate-rich elements within the 3' untranslated region of mRNA. Thus, tumors metabolically target naïve T cells to evade immunity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774333 | PMC |
| http://dx.doi.org/10.1126/sciimmunol.aan4631 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Integer Topological Defects Reveal Antisymmetric Forces in Active Nematics.
Phys Rev Lett
December 2024
Shanghai Jiao Tong University, School of Physics and Astronomy, Institute of Natural Sciences, Shanghai 200240, China.
Cell layers are often categorized as contractile or extensile active, nematics but recent experiments on neural progenitor cells with induced +1 topological defects challenge this classification. In a bottom-up approach, we first study a relevant particle-level model and then analyze a continuum theory derived from it. We show that both model and theory account qualitatively for the main experimental result, i.
View Article and Find Full Text PDFA mitochondria-targeted iridium(III) complex-based sensor for endogenous GSH detection in living cells.
Analyst
January 2025
Jiangxi Provincial Key Laboratory of Organic Functional Molecules; Institute of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China.
Glutathione (GSH) plays an important role in maintaining redox homeostasis in biological systems. Development of reliable glutathione sensors is of great significance to better understand the role of biomolecules in living cells and organisms. Based on the advantages of the photophysical properties of iridium complexes, we proposed a "turn-on" phosphorescent sensor.
View Article and Find Full Text PDFIn Vitro Culturing Technique for Studying Cellular Dynamics in Zebrafish Scales.
J Vis Exp
January 2025
Department of Biology, Mount Saint Vincent University;
Zebrafish scales offer a variety of advantages for use in standard laboratories for teaching and research purposes. Scales are easily collected without the need for euthanasia, regenerate within a couple of weeks, and are translucent and small, allowing them to be viewed using a standard microscope. Zebrafish scales are especially useful in educational environments, as they provide a unique opportunity for students to engage in hands-on learning experiences, particularly in understanding cellular dynamics and in vitro culturing methods.
View Article and Find Full Text PDFQuantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD).
J Vis Exp
January 2025
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Henry and Allison McCance Center for Brain Health, Department of Neurology, Massachusetts General Hospital, Harvard Medical School;
A method to quantitate the stabilization of Mitochondria-Associated endoplasmic reticulum Membranes (MAMs) in a 3-dimensional (3D) neural model of Alzheimer's disease (AD) is presented here. To begin, fresh human neuro progenitor ReN cells expressing β-amyloid precursor protein (APP) containing familial Alzheimer's disease (FAD) or naïve ReN cells are grown in thin (1:100) Matrigel-coated tissue culture plates. After the cells reach confluency, these are electroporated with expression plasmids encoding red fluorescence protein (RFP)-conjugated mitochondria-binding sequence of AKAP1(34-63) (Mito-RFP) that detects mitochondria or constitutive MAM stabilizers MAM 1X or MAM 9X that stabilize tight (6 nm ± 1 nm gap width) or loose (24 nm ± 3 nm gap width) MAMs, respectively.
View Article and Find Full Text PDFProximity Ligation Assay to Study Oncogene-Derived Transcription-Replication Conflicts.
J Vis Exp
January 2025
Institute of Biochemistry and Molecular Biology, Hengyang Medical School, University of South China; National Health Commission Key Laboratory of Birth Defect Research and Preventio, Hunan Provincial Maternal and Child Health Care Hospital;
Both DNA replication and RNA transcription utilize genomic DNA as their template, necessitating spatial and temporal separation of these processes. Conflicts between the replication and transcription machinery, termed transcription-replication conflicts (TRCs), pose a considerable risk to genome stability, a critical factor in cancer development. While several factors regulating these collisions have been identified, pinpointing primary causes remains difficult due to limited tools for direct visualization and clear interpretation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!