Pyruvate dehydrogenase complex is a crucial enzyme involved in the oxidation of glucose. It is regulated by pyruvate dehydrogenase kinase (PDHK) and pyruvate dehydrogenase phosphatase. Studies have demonstrated that PDHK1, a key enzyme in glucose metabolism, behaves like oncogenes. It is highly expressed in tumors and is associated with poor patient prognosis. However, there is limited research on how PDHK1 affects immune cell function. We have established a model of NK cell exhaustion to investigate the impact of dichloroacetate (DCA) on NK cell function. The production of granzyme B, IFNγ, TNFα, and CD107a by NK cells was explored by flow cytometry. The real-time live-cell imaging system was used to monitor the ability of NK cells against tumor cells. The Seahorse analyzer was utilized to measure the oxygen consumption rate and extracellular acidification rate of NK cells. A mouse model was used to investigate the potential of combining DCA with adjuvant NK cell infusion. Our study demonstrated that the hepatocellular carcinoma microenvironment mediated NK cellular exhaustion and high expression of PDHK1 and reduced cytokine secretion. We discovered that the PDHK1 inhibitor DCA enhances the activity and function of exhausted NK cells infiltrating the tumor microenvironment. Furthermore, in a s.c. hepatocellular carcinoma mouse model, DCA combined with NK cell treatment resulted in retarding cancer progression. This study indicates the potential of DCA in rescuing NK cell exhaustion and eliciting antitumor immunity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1158/1535-7163.MCT-24-0222 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Tension-induced organelle stress: an emerging target in fibrosis.
Trends Pharmacol Sci
January 2025
Department of Surgery, University of California, San Francisco, San Francisco, CA, USA; Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA, USA; UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA; Department of Radiation Oncology, Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
Fibrosis accounts for approximately one-third of disease-related deaths globally. Current therapies fail to cure fibrosis, emphasizing the need to identify new antifibrotic approaches. Fibrosis is defined by the excessive accumulation of extracellular matrix (ECM) and resultant stiffening of tissue stroma.
View Article and Find Full Text PDFTemporal dynamics of PM induced cell death: Emphasizing inflammation as key mediator in the late stages of prolonged myocardial toxicity.
Exp Cell Res
January 2025
Cardiovascular Center, College of Medicine, University of Cincinnati, Ohio-45267, United States of America; School of Chemical and Biotechnology, SASTRA Deemed University, Tirumalaisamudram, Thanjavur-613401, Tamil Nadu, India. Electronic address:
Multiple forms of cell death contribute significantly to cardiovascular pathologies, negatively impacting cardiac remodeling and leading to heart failure. While myocardial cell death has been associated with PM induced cardiotoxicity, the temporal dynamics of various cell death forms, such as apoptosis, ferroptosis, necroptosis, and pyroptosis, in relation to inflammatory processes, remain underexplored. This study examines the time-dependent onset and progression of these cell death pathways in the myocardium and their correlation with inflammation in a Wistar rat model.
View Article and Find Full Text PDFSTAT3 Orchestrates Immune Dynamics in Hepatocellular Carcinoma: A Pivotal Nexus in Tumor Progression.
Crit Rev Oncol Hematol
January 2025
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Precision Radiation Oncology, Hubei, China.
Hepatocellular carcinoma (HCC) presents a formidable challenge in oncology, attributed to its association with chronic liver diseases and global prevalence. The immune microenvironment profoundly influences HCC progression, balancing immune suppression and antitumor responses. The Signal Transducer and Activator of Transcription 3 (STAT3) is central to this equilibrium, orchestrating immune dynamics and intertwining tumor progression with immune evasion mechanisms.
View Article and Find Full Text PDFPhosphorylated-tau associates with HSV-1 chromatin and correlates with nuclear speckles decondensation in low-density host chromatin regions.
Neurobiol Dis
January 2025
Department of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, FL 32611, USA.
Abnormal tau phosphorylation is a key mechanism in neurodegenerative diseases. Evidence implicates infectious agents, such as Herpes Simplex Virus 1 (HSV-1), as co-factors in the onset or the progression of neurodegenerative diseases, including Alzheimer's disease. This has led to divergence in the field regarding the contribution of viruses in the etiology of neurodegenerative diseases.
View Article and Find Full Text PDFPreparation of Anterolateral Thigh Flap from Polio-Affected Lower Limb: A Safe Surgical Option that Preserves Patient's Motor Function.
J Stomatol Oral Maxillofac Surg
January 2025
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, 430079, Wuhan, P.R. China; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, 430079, Wuhan, P.R. China. Electronic address:
The anterolateral thigh (ALT) flap is a commonly used donor site for free tissue transfer, especially in head and neck reconstructions. The flap's success is primarily determined by the quality and quantity of its perforating vessels, which is why clinicians typically prefer harvesting from a healthy leg with intact vascular anatomy. Poliomyelitis typically causes unilateral lower limb paralysis, resulting in muscle atrophy and deformities.
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!