A clinical oncolytic herpes simplex virus (HSV) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), talimogene laherparepvec, causes regression of injected and non-injected melanoma lesions in patients and is now licensed for clinical use in advanced melanoma. To date, limited data are available regarding the mechanisms of human anti-tumor immune priming, an improved understanding of which could inform the development of future combination strategies with improved efficacy. This study addressed direct oncolysis and innate and adaptive human immune-mediated effects of a closely related HSV encoding GM-CSF (HSV) alone and in combination with histone deacetylase inhibition. We found that HSV supported activation of anti-melanoma immunity via monocyte-mediated type I interferon production, which activates NK cells, and viral maturation of immature dendritic cells (iDCs) into potent antigen-presenting cells for cytotoxic T lymphocyte (CTL) priming. Addition of the histone deacetylase inhibitor valproic acid (VPA) to HSV treatment of tumor cells increased viral replication, viral GM-CSF production, and oncolysis and augmented the development of anti-tumor immunity. Mechanistically, VPA increased expression of activating ligands for NK cell recognition and induced expression of tumor-associated antigens, supporting innate NK cell killing and CTL priming. These data support the clinical combination of talimogene laherparepvec with histone deacetylase inhibition to enhance oncolysis and anti-tumor immunity.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554638 | PMC |
http://dx.doi.org/10.1016/j.ymthe.2019.04.008 | DOI Listing |
Cardiovasc Res
January 2025
Department of Pathophysiology, Shenzhen University Medical School, Shenzhen 518060, China.
Aims: Decrease in repolarizing K+ currents, particularly the fast component of transient outward K+ current (Ito,f), prolongs action potential duration (APD) and predisposes the heart to ventricular arrhythmia during cardiac hypertrophy. Histone deacetylases (HDACs) have been suggested to participate in the development of cardiac hypertrophy, and class I HDAC inhibition has been found to attenuate pathological remodeling. This study investigated the potential therapeutic effects of HDAC2 on ventricular arrhythmia in pressure overload-induced cardiac hypertrophy.
View Article and Find Full Text PDFPLoS One
January 2025
Division of Oral Physiology, Faculty of Dentistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
This study examined the effects of treadmill running (TR) regimens on craniofacial pain- and anxiety-like behaviors, as well as their effects on neural changes in specific brain regions of male mice subjected to repeated social defeat stress (SDS) for 10 days. Behavioral and immunohistochemical experiments were conducted to evaluate the impact of TR regimens on SDS-related those behaviors, as well as epigenetic and neural activity markers in the anterior cingulate cortex (ACC), insular cortex (IC), rostral ventromedial medulla (RVM), and cervical spinal dorsal horn (C2). Behavioral responses were quantified using multiple tests, while immunohistochemistry measured histone H3 acetylation, histone deacetylases (HDAC1, HDAC2), and neural activity markers (FosB and phosphorylated cAMP response element-binding protein (pCREB).
View Article and Find Full Text PDFImmun Inflamm Dis
January 2025
Department of Medical Biochemistry, Institute of Health, Dambi Dollo University, Dambi Dolo, Ethiopia.
Background: The pathomechanism of blast traumatic brain injury (TBI) and blunt TBI is different. In blast injury, evidence indicates that a single blast exposure can often manifest long-term neurological impairments. However, its pathomechanism is still elusive, and treatments have been symptomatic.
View Article and Find Full Text PDFAmphetamines (AMPHs) are psychostimulants commonly used for the treatment of neuropsychiatric disorders. They are also misused (AMPH use disorder; AUD), with devastating outcomes. Recent studies have implicated dysbiosis in the pathogenesis of AUD.
View Article and Find Full Text PDFFront Immunol
January 2025
Acupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease. Patients with UC typically exhibit disruption of the Treg/Th17 immune axis, but its exact mechanism is still unclear.
Methods: This study first analyzed RNA- seq data from public databases of humans and mice, and cytology experiments were conducted to induce or inhibit the expression of SIRT1.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!