IL-15-secreting CAR natural killer cells directed toward the pan-cancer target CD70 eliminate both cancer cells and cancer-associated fibroblasts.

Background: It remains challenging to obtain positive outcomes with chimeric antigen receptor (CAR)-engineered cell therapies in solid malignancies, like colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC). A major obstacle is the lack of targetable surface antigens that are not shared by healthy tissues. CD70 emerges as interesting target, due to its stringent expression pattern in healthy tissue and its apparent role in tumor progression in a considerable amount of malignancies.

Clinical characterization of a hypersensitivity mixed bacterial and fungal dermatitis in a translational model of porcine NASH.

Introduction: The development of animal models of chronic liver disease via diet modification is a promising avenue for translational research but can lead to unexpected side effects that impact model adoption. While these side effects are well characterized in rodent models of nonalcoholic steatohepatitis (NASH), limited knowledge of these effects exists for novel porcine models of NASH. To close this gap, the present study investigates the side effects of diet-based NASH induction in pigs, with a systematic analysis of the pathologic mechanisms underlying dermatitis development and evaluation of treatment approaches.

The retrograde IFT dynein is required for normal function of diverse mechanosensory cilia in .

Introduction: Cilia biogenesis relies on intraflagellar transport (IFT), a conserved transport mechanism which functions bi-directionally to bring protein complexes to the growing ciliary tip and recycle signaling and transport proteins between the cilium and cell body. In , anterograde IFT is critical for assembly of sensory cilia in the neurons of both chordotonal (ch) organs, which have relatively long ciliary axonemes, and external sensory (es) organs, which have short axonemal segments with microtubules in distal sensory segments forming non-axonemal bundles. We previously isolated the () mutant in a mutagenesis screen for auditory mutants.

Undisclosed interference in 25-OH-Vitamin D immunoassay on Liaison XL analyzer when using heparin plasma tubes.

This study investigates the impact of sample type on the measurement of 25-OH-vitamin D using the Liaison XL (Diasorin) and Cobas e801 (Roche). This investigation was motivated by the need to optimize sample volume usage, which led us to adopt the use of heparin plasma, an alternative proposed by Diasorin in their specification. Discordant and unexplainable results were observed, prompting us to evaluate the effect of sample type on the accuracy of the 25-OH-vitamin D measurements.

Role of miR-204 in segmental cardiac effects of phenylephrine and pressure overload.

Cardiotoxicity caused by adrenergic receptor agonists overdosing or stress-induced catecholamine release promotes cardiomyopathy, resembling Takotsubo cardiomyopathy (TC). TC is characterized by transient regional systolic dysfunction of the left ventricle. The animal models of TC and modalities for assessing regional wall motion abnormalities in animal models are lacking.

Site-specific Ga-labeled nanobody for PET imaging of CD70 expression in preclinical tumor models.

Background: CD70-CD27 is a costimulatory ligand-receptor pair in the tumor necrosis factor receptor family. With only limited expression in normal tissues, CD70 is constitutively expressed in a variety of solid tumors and hematologic malignancies, facilitating immunosuppression through CD27 signaling in the tumor microenvironment by enhanced survival of regulatory T cells, induction of T cell apoptosis, and T cell exhaustion. Consequently, CD70 is an increasingly recognized target for developing antibody-based therapies, but its expression patterns vary among different tumor types in spatial distribution, magnitude of expression and percentage of positive cells.

Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer.

Despite the recent emergence of immune checkpoint inhibitors, clinical outcomes of metastatic NSCLC patients remain poor, pointing out the unmet need to develop novel therapies to enhance the anti-tumor immune response in NSCLC. In this regard, aberrant expression of the immune checkpoint molecule CD70 has been reported on many cancer types, including NSCLC. In this study, the cytotoxic and immune stimulatory potential of an antibody-based anti-CD70 (aCD70) therapy was explored as single agent and in combination with docetaxel and cisplatin in NSCLC and .

The prognostic impact of the immune signature in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors that retain their poor prognosis despite recent advances in their standard of care. As the involvement of the immune system against HNSCC development is well-recognized, characterization of the immune signature and the complex interplay between HNSCC and the immune system could lead to the identification of novel therapeutic targets that are required now more than ever. In this study, we investigated RNA sequencing data of 530 HNSCC patients from The Cancer Genome Atlas (TCGA) for which the immune composition (CIBERSORT) was defined by the relative fractions of 10 immune-cell types and expression data of 45 immune checkpoint ligands were quantified.

Behavioral Parent Training for Families With Young Deaf or Hard of Hearing Children Followed in Hearing Health Care.

Purpose: It is well established that individuals with a communication disability, including being deaf or hard of hearing (DHH), experience inequities in health services and outcomes. These inequities extend to DHH children's access to psychosocial evidence-based interventions (EBIs). Behavioral parent training is an EBI that can be used to improve caregiver and child outcomes.

Communities Helping the Hearing of Infants by Reaching Parents (CHHIRP) through patient navigation: a hybrid implementation effectiveness stepped wedge trial protocol.

Introduction: As the most common neonatal sensory disorder in the USA, infant hearing loss has an incidence of 1.7 per 1000 births. The consequences of delayed diagnosis and failure to obtain timely intervention include significant communication impairment and negative socioeconomic effects.

Study Protocol: Type 1 Hybrid Effectiveness-Implementation Trial of a Behavioral Parent Training Intervention for Parents of Young Children Who Are Deaf or Hard of Hearing.

Purpose: Children who are deaf or hard of hearing (DHH) and who use hearing aids or cochlear implants are more likely than their peers with typical hearing to exhibit behavior problems. Although multiple evidence-based interventions for child behavior problems exist, they are rarely delivered to children who are DHH, and no rigorous randomized controlled trials have been conducted to determine their effects with this population. This protocol describes a study aiming to test the effectiveness of an evidence-based behavioral parent training intervention adapted for parents of young children who are DHH and simultaneously to assess key implementation outcomes and multilevel contextual factors influencing implementation.

The CD70-CD27 axis in oncology: the new kids on the block.

The immune checkpoint molecule CD70 and its receptor CD27 are aberrantly expressed in many hematological and solid malignancies. Dysregulation of the CD70-CD27 axis within the tumor and its microenvironment is associated with tumor progression and immunosuppression. This is in contrast to physiological conditions, where tightly controlled expression of CD70 and CD27 plays a role in co-stimulation in immune responses.

Cusatuzumab for treatment of CD70-positive relapsed or refractory cutaneous T-cell lymphoma.

Background: The clinical benefit of cusatuzumab, a CD70-directed monoclonal antibody with enhanced effector functions, was investigated in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL).

Methods: In this cohort expansion of the ARGX-110-1201 study, 27 patients with R/R CTCL received cusatuzumab at 1 (n = 11) or 5 mg/kg (n = 16) once every 3 weeks to investigate its safety, dose, and exploratory efficacy. The pharmacokinetics, immunogenicity, CD70 expression, and CD70/CD27 biology were also assessed.

The NHance Mutation-Equipped Anti-MET Antibody ARGX-111 Displays Increased Tissue Penetration and Anti-Tumor Activity in Advanced Cancer Patients.

Dysregulation of MET signaling has been implicated in tumorigenesis and metastasis. ARGX-111 combines complete blockade of this pathway with enhanced tumor cell killing and was investigated in 24 patients with MET-positive advanced cancers in a phase 1b study at four dose levels (0.3-10 mg/kg).

Parent and Provider Preferences for Parenting Intervention Delivery in Rural Appalachia: A Qualitative Analysis Guiding Adaptation.

The public health impact of behavioral parent training (BPT) is limited, especially in underserved communities such as rural central Appalachia. To improve access to BPT in this region, we completed the first two steps of the ADAPT-ITT framework for systematic adaptation of evidence-based interventions: (1) assessing community perspectives about BPT delivery, and (2) deciding upon a specific intervention and adaptations needed to increase its acceptability and accessibility in rural central Appalachian counties. Guided by a community advisory board, we conducted key informant interviews with parents (N = 21) and three focus groups with child service providers to elicit stakeholders' perspectives about child behavior problems in their communities; existing resources; and preferences regarding four characteristics of BPT delivery: interventionist, modality, dose, and location.

Fatigue and physical activity: Potential modifiable contributors to parenting sense of competence.

Objectives: Parenting sense of competence, as measured by the Parenting Sense of Competence Scale (PSCS), is defined as one's levels of satisfaction and self-efficacy experienced in the parenting role. Previous studies have identified significant associations among PSCS scores and a host of parenting characteristics predictive of child outcomes. Existing approaches to improving parenting sense of competence focus on developing parenting knowledge and skills; however, other modifiable contributing factors to parenting sense of competence may exist.

Clinically Relevant Chemotherapeutics Have the Ability to Induce Immunogenic Cell Death in Non-Small Cell Lung Cancer.

The concept of immunogenic cell death (ICD) has emerged as a cornerstone of therapy-induced anti-tumor immunity. To this end, the following chemotherapies were evaluated for their ability to induce ICD in non-small cell lung cancer (NSCLC) cell lines: docetaxel, carboplatin, cisplatin, oxaliplatin and mafosfamide. The ICD hallmarks ATP, ecto-calreticulin, HMGB1, phagocytosis and maturation status of dendritic cells (DCs) were assessed in vitro.

Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients.

(1) Background: Therapeutic blocking of the interaction between programmed death-1 (PD-1) with its ligand PD-L1, an immune checkpoint, is a promising approach to restore the antitumor immune response. Improved clinical outcomes have been shown in different human cancers, including non-small cell lung cancer (NSCLC). Unfortunately, still a high number of NSCLC patients are treated with immunotherapy without obtaining any clinical benefit, due to the limitations of PD-L1 protein expression as the currently sole predictive biomarker for clinical use; (2) Methods: In this study, we applied mass spectrometry imaging (MSI) to discover new protein biomarkers, and to assess the possible correlation between candidate biomarkers and a positive immunotherapy response by matrix-assisted laser desorption/ionization (MALDI) MSI in 25 formalin-fixed paraffin-embedded (FFPE) pretreatment tumor biopsies (Biobank@UZA); (3) Results: Using MALDI MSI, we revealed that the addition of neutrophil defensin 1, 2 and 3 as pretreatment biomarkers may more accurately predict the outcome of immunotherapy treatment in NSCLC.

Specialized Blood Collection Tubes for Liquid Biopsy: Improving the Pre-analytical Conditions.

Introduction: The potential of circulating cell-free DNA (cfDNA) analysis as a liquid biopsy has led to the development of several specialized measuring tools. Interest in the (pre-)analytical conditions of the liquid biopsy workflow has increased over the past few years.

Methods: In this study, we performed a systematic review of the cfDNA stabilizing efficacy in standard EDTA and specialized blood collection tubes (BCTs), namely CellSave, Norgen, PAXgene, Roche, and Streck tubes, and compared the efficacy of the latter three BCTs in a situation resembling the clinical setting.

Radiosensitization of Non-Small Cell Lung Cancer Cells by the Plk1 Inhibitor Volasertib Is Dependent on the p53 Status.

Polo-like kinase 1 (Plk1), a master regulator of mitotic cell division, is highly expressed in non-small cell lung cancer (NSCLC) making it an interesting drug target. We examined the in vitro therapeutic effects of volasertib, a Plk1 inhibitor, in combination with irradiation in a panel of NSCLC cell lines with different p53 backgrounds. Pretreatment with volasertib efficiently sensitized p53 wild type cells to irradiation.

Screening a Broad Range of Solid and Haematological Tumour Types for CD70 Expression Using a Uniform IHC Methodology as Potential Patient Stratification Method.

The constitutive expression of CD70 has been described in various haematological and solid tumour types. In addition, the co-expression of its receptor in tumours has been demonstrated, mediating tumour cell proliferation. Although CD70 expression is a prerequisite to enrol patients in solid tumour clinical trials using anti-CD70 immunotherapy, there is currently no standardised test to evaluate CD70 expression.

Cold Atmospheric Plasma-Treated PBS Eliminates Immunosuppressive Pancreatic Stellate Cells and Induces Immunogenic Cell Death of Pancreatic Cancer Cells.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with a low response to treatment and a five-year survival rate below 5%. The ineffectiveness of treatment is partly because of an immunosuppressive tumor microenvironment, which comprises tumor-supportive pancreatic stellate cells (PSCs). Therefore, new therapeutic strategies are needed to tackle both the immunosuppressive PSC and pancreatic cancer cells (PCCs).

The potential and controversy of targeting STAT family members in cancer.

The Signal Transducer and Activator of Transcription (STAT) family of proteins consists of transcription factors that play a complex and essential role in the regulation of physiologic cell processes, such as proliferation, differentiation, apoptosis and angiogenesis, and serves to organize the epigenetic landscape of immune cells. To date, seven STAT genes have been identified in the human genome; STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. They all account for diverse effects in response to extracellular signaling proteins, mainly by altering gene transcription in the effector cells.