Reprogrammed IDO-Induced Immunosuppressive Microenvironment Synergizes with Immunogenic Magnetothermodynamics for Improved Cancer Therapy.

Indoleamine 2,3-dioxygenase (IDO), highly expressed in hepatocellular carcinoma (HCC), plays a pivotal role in creating an immune-suppressive tumor microenvironment. Inhibiting IDO activity has emerged as a promising immunotherapeutic strategy; however, the delivery of IDO inhibitors to the tumor site is constrained, limiting their therapeutic efficacy. In this study, we developed a magnetic vortex nanodelivery system for the targeted delivery of the IDO inhibitor NLG919, integrated with magnetic hyperthermia therapy to reverse the immune-suppressive microenvironment of liver cancer and inhibit tumor growth. This system comprises thermoresponsive polyethylenimine-coated ferrimagnetic vortex-domain iron oxide nanorings (PI-FVIOs) loaded with NLG919 (NLG919/PI-FVIOs). Under thermal effects, NLG919 can be precisely released from the delivery system, counteracting IDO-mediated immune suppression and synergizing with NLG919/PI-FVIOs-mediated magnetothermodynamic (MTD) therapy-induced immunogenic cell death (ICD), resulting in effective HCC suppression. In vivo studies demonstrate that this combination therapy significantly inhibits tumor growth and metastasis by enhancing the accumulation of cytotoxic T lymphocytes and suppressing regulatory T cells within the tumor. Overall, our findings reveal that NLG919/PI-FVIOs can induce a potent antitumor immune response by disrupting the IDO pathway and activating the ICD, offering a promising therapeutic avenue for HCC treatment.

Intracellular magnetic hyperthermia reverses sorafenib resistance in hepatocellular carcinoma through its action on signaling pathways.

Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), unfortunately encounters resistance in most patients, leading to disease progression. Traditional approaches to counteract this resistance, particularly those targeting the RAF-MEK-ERK pathway, often face clinical feasibility limitations. Magnetic hyperthermia (MH), unlike conventional thermal therapies, emerges as a promising alternative. It uniquely combines magnetothermal effects with an increase in reactive oxygen species (ROS). This study found the potential of intracellular MH enhanced the efficacy of sorafenib, increased cellular sensitivity to sorafenib, and reversed sorafenib resistance by inhibiting the RAF-MEK-ERK pathway in an ROS-dependent manner in a sorafenib-resistant HCC cell. Further, in a sorafenib-resistant HCC mouse model, MH significantly sensitized tumors to sorafenib therapy, resulting in inhibited tumor growth and improved survival rates. This presents a promising strategy to overcome sorafenib resistance in HCC, potentially enhancing therapeutic outcomes for patients with this challenging condition.

Autoimmune Glial Fibrillary Acidic Protein (Gfap) Astrocytopa-Thy Accompanied with Reversible Splenial Lesion Syndrome (RESLES): A Case Report and Literature Review.

BACKGROUND: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy usually presents as meningoencephalomyelitis. Many patients developed flu-like symptoms preceding the neurologic symptoms. Reversible lesion in the splenium of the corpus callosum (SCC) is a clinical and radiological syndrome secondary to many kinds of etiologies, including infections, which is termed RESLES. CASE PRESENTATION: we reported a case developing irregularly high fever, both temporal pain, low limbs fatigue with frequent urination admitted to our neurology department. CSF test showed GFAP-IgG positive, elevated WBC counts and protein, with low glucose and chlorine, while MRI showed a reversible lesion on SCC, leading us to diagnose autoimmune GFAP autocytopathy accompanied with RESLES. The boy had significantly improved after anti-virus and steroids therapy. DISCUSSION: Autoimmune GFAP autocytopathy accompanied with RESLES is rarely seen, and pathogenesis for the co-existence has not been clarified. Autoimmune GFAP autocytopathy and RESLES are both related to viral infection. Our case covered infectious symptoms and improved after antiviral treatment, suggesting virus infection may perform a key role in pathogenesis.