Development of a murine laser interstitial thermotherapy system.

Objective: The objective of this study was to develop a murine system for the delivery of laser interstitial thermotherapy (LITT) with probe-based thermometry as a model for human glioblastoma treatment to investigate thermal diffusion in heterogeneous brain tissue.

Methods: First, the tissue heating properties were characterized using a diode-pumped solid-state near-infrared laser in a homogeneous tissue model. The laser was adapted for use with a repurposed stereotactic surgery frame utilizing a micro laser probe and Hamilton syringe.

mRNA aggregates harness danger response for potent cancer immunotherapy.

Messenger RNA (mRNA) has emerged as a remarkable tool for COVID-19 prevention but its use for induction of therapeutic cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Herein, we develop a facile approach for substantially enhancing immunogenicity of tumor-derived mRNA in lipid-particle (LP) delivery systems. By using mRNA as a molecular bridge with ultrapure liposomes and foregoing helper lipids, we promote the formation of 'onion-like' multi-lamellar RNA-LP aggregates (LPA).

mRNA challenge predicts brain cancer immunogenicity and response to checkpoint inhibitors.

To prospectively determine whether brain tumors will respond to immune checkpoint inhibitors (ICIs), we developed a novel mRNA vaccine as a viral mimic to elucidate cytokine release from brain cancer cells in vitro. Our results indicate that cytokine signatures following mRNA challenge differ substantially from ICI responsive versus non-responsive murine tumors. These findings allow for creation of a diagnostic assay to quickly assess brain tumor immunogenicity, allowing for informed treatment with ICI or lack thereof in poorly immunogenic settings.

Gene Expression in Renal Transplantation Patients.

Background: It has been well-documented that the Fc receptor-like (FCRL) molecule contributes to the pathogenesis of certain autoimmune disorders. FCRL molecules belong to the immunoglobulin superfamily produced by B cells. Also, these molecules induce activating or inhibitory signals of B cells.

Optimizing T Cell-Based Therapy for Glioblastoma.

Evading T cell surveillance is a hallmark of cancer. Patients with solid tissue malignancy, such as glioblastoma (GBM), have multiple forms of immune dysfunction, including defective T cell function. T cell dysfunction is exacerbated by standard treatment strategies such as steroids, chemotherapy, and radiation.

Metabolomics Monitoring of Treatment Response to Brain Tumor Immunotherapy.

Immunotherapy has revolutionized care for many solid tissue malignancies, and is being investigated for efficacy in the treatment of malignant brain tumors. Identifying a non-invasive monitoring technique such as metabolomics monitoring to predict patient response to immunotherapy has the potential to simplify treatment decision-making and to ensure therapy is tailored based on early patient response. Metabolomic analysis of peripheral immune response is feasible due to large metabolic shifts that immune cells undergo when activated.

Adult immuno-oncology: using past failures to inform the future.

In oncology, "immunotherapy" is a broad term encompassing multiple means of utilizing the patient's immune system to combat malignancy. Prominent among these are immune checkpoint inhibitors, cellular therapies including chimeric antigen receptor T-cell therapy, vaccines, and oncolytic viruses. Immunotherapy for glioblastoma (GBM) has had mixed results in early trials.

Comparing Standard Performance and Outcome Measures in Hospitalized Pituitary Tumor Patients with Secretory versus Nonsecretory Tumors.

Background: Patient safety indicators (PSIs) and hospital-acquired conditions (HACs) are reported quality measures. We compared their prevalence in patients with secretory and nonsecretory pituitary adenoma using the National (Nationwide) Inpatient Sample (NIS), Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality.

Methods: The NIS was queried for hospitalizations 2002-2014 involving pituitary adenomas.

Sarcosine promotes trafficking of dendritic cells and improves efficacy of anti-tumor dendritic cell vaccines via CXC chemokine family signaling.

Background: Dendritic cell (DC) vaccine efficacy is directly related to the efficiency of DC migration to the lymph node after delivery to the patient. We discovered that a naturally occurring metabolite, sarcosine, increases DC migration in human and murine cells resulting in significantly improved anti-tumor efficacy. We hypothesized that sarcosine induced cell migration was due to chemokine signaling.

Dysregulation of Glutamate Transport Enhances Treg Function That Promotes VEGF Blockade Resistance in Glioblastoma.

Anti-VEGF therapy prolongs recurrence-free survival in patients with glioblastoma but does not improve overall survival. To address this discrepancy, we investigated immunologic resistance mechanisms to anti-VEGF therapy in glioma models. A screening of immune-associated alterations in tumors after anti-VEGF treatment revealed a dose-dependent upregulation of regulatory T-cell (Treg) signature genes.

CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors.

Chimeric antigen receptor (CAR) T-cell therapy targeting solid tumors has stagnated as a result of tumor heterogeneity, immunosuppressive microenvironments, and inadequate intratumoral T cell trafficking and persistence. Early (≤3 days) intratumoral presentation of CAR T cells post-treatment is a superior predictor of survival than peripheral persistence. Therefore, we have co-opted IL-8 release from tumors to enhance intratumoral T-cell trafficking through a CAR design for maximal antitumor activity in solid tumors.

Effect of Timing and Complement Receptor Antagonism on Intragraft Recruitment and Protolerogenic Effects of Mesenchymal Stromal Cells in Murine Kidney Transplantation.

Background: Mesenchymal stromal cells (MSCs) have protolerogenic effects in renal transplantation, but they induce long-term regulatory T cells (Treg)-dependent graft acceptance only when infused before transplantation. When given posttransplant, MSCs home to the graft where they promote engraftment syndrome and do not induce Treg. Unfortunately, pretransplant MSC administration is unfeasible in deceased-donor kidney transplantation.

Ultrasound wave assisted removal of Ceftriaxone sodium in aqueous media with novel nano composite g-CN/MWCNT/BiWO based on CCD-RSM model.

The aim of this study was ultrasound assisted removal of Ceftriaxone sodium (CS) based on CCD model. Using sonochemical synthesized BiWO implanted on graphitic carbon nitride/Multiwall carbon nanotube (g-CN/MWCNT/BiWO). For this purpose g-CN/MWCNT/BiWO was synthesized and characterized using diverse approaches including XRD, FE-SEM, XPS, EDS, HRTEM, FT-IR.

Modulation of temozolomide dose differentially affects T-cell response to immune checkpoint inhibition.

Background: The changes induced in host immunity and the tumor microenvironment by chemotherapy have been shown to impact immunotherapy response in both a positive and a negative fashion. Temozolomide is the most common chemotherapy used to treat glioblastoma (GBM) and has been shown to have variable effects on immune response to immunotherapy. Therefore, we aimed to determine the immune modulatory effects of temozolomide that would impact response to immune checkpoint inhibition in the treatment of experimental GBM.

The role of CMV in glioblastoma and implications for immunotherapeutic strategies.

Controversy surrounds the role of cytomegalovirus (CMV) in glioblastoma (GBM). However, several studies have shown that CMV nucleic acids and proteins are present within GBM tumor tissue. CMV has been implicated in GBM pathogenesis by affecting tumor stem cell factors, angiogenesis and immune pathways.

Personalized Tumor RNA Loaded Lipid-Nanoparticles Prime the Systemic and Intratumoral Milieu for Response to Cancer Immunotherapy.

Translation of nanoparticles (NPs) into human clinical trials for patients with refractory cancers has lagged due to unknown biologic reactivities of novel NP designs. To overcome these limitations, simple well-characterized mRNA lipid-NPs have been developed as cancer immunotherapeutic vaccines. While the preponderance of RNA lipid-NPs encoding for tumor-associated antigens or neoepitopes have been designed to target lymphoid organs, they remain encumbered by the profound intratumoral and systemic immunosuppression that may stymie an activated T cell response.

Temozolomide for immunomodulation in the treatment of glioblastoma.

Temozolomide is the most widely used chemotherapy for patients with glioblastoma (GBM) despite the fact that approximately half of treated patients have temozolomide resistance and all patients eventually fail therapy. Due to the limited efficacy of existing therapies, immunotherapy is being widely investigated for patients with GBM. However, initial immunotherapy trials in GBM patients have had disappointing results as monotherapy.

The IDH1 Mutation-Induced Oncometabolite, 2-Hydroxyglutarate, May Affect DNA Methylation and Expression of PD-L1 in Gliomas.

Malignant gliomas are heterogeneous brain tumors with the potential for aggressive disease progression, as influenced by suppressive immunoediting. Given the success and enhanced potential of immune-checkpoint inhibitors in immunotherapy, we focused on the connections between genetic alterations affected by IDH1 mutations and immunological landscape changes and PDL-1 expression in gliomas. Paired surgically resected tumors from lower-grade gliomas (LGGs) and glioblastomas (GBM) were investigated, and a genetic analysis of patients' primary tumor samples culled from TCGA datasets was performed.

Evaluation of Immunomodulatory Effects of Mesenchymal Stem Cells Soluble Factors on miR-155 and miR-23b Expression in Mice Dendritic Cells.

Mesenchymal stem cells (MSCs) can modulate dendritic cells (DCs) activation and induce tolerogenic characteristics in DCs. All mechanisms involved in MSCs-induced tolerogenic DCs are not fully understood. MicroRNAs (miRs) play important role in maturation and function of DCs.