Anti-PD1 therapies induce an early expansion of Ki67CD8 T cells in metastatic non-oncogene addicted NSCLC patients.

Pembrolizumab (an anti-PD1 antibody) alone or combined with chemotherapy represented the standard of care for advanced non-oncogene addicted non-small cell lung cancer (NSCLC) patients. These therapies induced early modifications of the immune response impacting the clinical outcome. Identifying early changes in the immune system was critical to directing the therapeutic choice and improving the clinical outcome.

Exploring Genomic Biomarkers for Pembrolizumab Response: A Real-World Approach and Patient Similarity Network Analysis Reveal DNA Response and Repair Gene Mutations as a Signature.

: Single-agent immune checkpoint inhibitor (IO) therapy is the standard for non-oncogene-addicted advanced non-small cell lung cancer (aNSCLC) with PD-L1 tumor proportion score ≥ 50%. Smoking-induced harm generates high tumor mutation burden (H-TMB) in smoking patients (S-pts), while never-smoking patients (NS-pts) typically have low TMB (L-TMB) and are unresponsive to IO. However, the molecular characterization of NS-pts with H-TMB remains unclear.

Exploring pharmacokinetic variability of palbociclib in HR+/HER2- metastatic breast cancer: a focus on age, renal function, and drug-gene interactions.

Palbociclib, an oral inhibitor of cyclin-dependent kinase 4 and 6, is approved for the treatment of metastatic breast cancer. This study investigated the influence of diverse clinical and biological factors-age, renal function, genetic variations, and concomitant medications ()-on palbociclib pharmacokinetics. Employing a validated LC-MS/MS method, we analyzed the minimum plasma concentrations (C) of palbociclib in 68 women and determined the percentage deviations from the median C for each dosage group.

Precision oncology targeting FGFRs: A systematic review on pre-clinical activity and clinical outcomes of pemigatinib.

Fibroblast Growth Factor Receptors (FGFRs) are emerging as key factors involved in tumorigenesis, tumor microenvironment remodeling and acquired resistance to targeted therapies. Pemigatinib is a Tyrosine-Kinase Inhibitor that selectively targets aberrant FGFR1, FGFR2 and FGFR3. Pemigatinib is now approved for advanced-stage cholangiocarcinoma (CCA) but data suggests that other tumor histotypes exhibit FGFR alterations, thus hypothesizing its potential efficacy in other cancer settings.

Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma.

Immunosuppressive macrophages restrict anti-cancer immunity in glioblastoma (GBM). Here, we studied the contribution of microglia (MGs) and monocyte-derived macrophages (MDMs) to immunosuppression and mechanisms underlying their regulatory function. MDMs outnumbered MGs at late tumor stages and suppressed T cell activity.

Multiple congenital ocular anomalies in three related litters of Jack Russell Terrier puppies.

Objective: To describe multiple congenital ocular anomalies in three litters of Jack Russell Terrier puppies.

Animals Studied: Seven purebred Jack Russell Terrier puppies from three related litters and their four parents.

Procedures: Medical records of the puppies and their parents were evaluated.

CD137 and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line.

Background: Immune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approximately 20% of patients, highlighting the need to identify novel biomarkers to optimize treatment strategies. In several solid tumors, immune soluble factors, the activatory CD137 Tcells, and the immunosuppressive cell subsets Tregs and MDSCs (PMN(Lox1)-MDSC and M-MDSCs) correlated with responses to ICIs and clinical outcomes thus becoming appealing predictive and prognostic factors.

Targeting FGFRs by pemigatinib induces G1 phase cell cycle arrest, cellular stress and upregulation of tumor suppressor microRNAs.

Background: Fibroblast growth factor receptor (FGFR) gene family alterations are found in several cancers, indicating their importance as potential therapeutic targets. The FGFR-tyrosine kinase inhibitor (TKI) pemigatinib has been introduced in the treatment of advanced cholangiocarcinoma and more recently for relapsed or refractory myeloid/lymphoid neoplasms with FGFR2 and FGFR1 rearrangements, respectively. Several clinical trials are currently investigating the possible combination of pemigatinib with immunotherapy.

A network approach to define the predictive role of immune profile on tumor response and toxicity of anti PD-1 single agent immunotherapy in patients with solid tumors.

Background: The immune profile of each patient could be considered as a portrait of the fitness of his/her own immune system. The predictive role of the immune profile in immune-related toxicities (irAEs) development and tumour response to treatment was investigated.

Methods: A prospective, multicenter study evaluating, through a multiplex assay, the soluble immune profile at the baseline of 53 patients with advanced cancer, treated with immunotherapy as single agent was performed.

Effective bioremediation of clarithromycin and diclofenac in wastewater by microbes and Arundo donax L.

Bioremediation of pharmaceuticals has gained large research efforts, but there is still a need to improve the performance of bioremediation systems by selecting effective organisms. In this study, we characterized the capability to remove clarithromycin (CLA) and diclofenac (DCF) by the bacterium Streptomyces rochei, and the fungi Phanerochaete chrysosporium and Trametes versicolor. The macrolide antibiotic CLA and the non-steroid anti-inflammatory DCF were selected because these are two of the most frequently detected drugs in water bodies.

Membrane and Soluble CD137 in Systemic Lupus Erythematosus: Role as Biomarkers for Disease Activity.

Objective: The role of T cells in the pathogenesis of systemic lupus erythematosus (SLE) has recently gained attention. Costimulatory molecules are membrane proteins strictly associated with T-cell receptor (TCR), acting by activating or inhibiting T cells and antigen-presenting cells (APC) through direct and reverse signaling, thus becoming responsible for the development of effector T cells or regulatory T cells. The primary objective of the present case-control study was to evaluate the cell membrane expression of CD137 on T cells and the serum concentration of CD137 (sCD137) in a SLE cohort.

Circulating CD137 T Cell Levels Are Correlated with Response to Pembrolizumab Treatment in Advanced Head and Neck Cancer Patients.

Pembrolizumab, an anti-PD-1 antibody, has been approved as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma ((R/M) HNSCC). However, only a minority of patients benefit from immunotherapy, which highlights the need to identify novel biomarkers to optimize treatment strategies. CD137 T cells have been identified as tumour-specific T cells correlated with immunotherapy responses in several solid tumours.

Immune-related toxicity and soluble profile in patients affected by solid tumors: a network approach.

Background: Immune checkpoint inhibitors (ICIs) have particular, immune-related adverse events (irAEs), as a consequence of interfering with self-tolerance mechanisms. The incidence of irAEs varies depending on ICI class, administered dose and treatment schedule. The aim of this study was to define a baseline (T0) immune profile (IP) predictive of irAE development.

Soluble PD-L1 as a Prognostic Factor for Immunotherapy Treatment in Solid Tumors: Systematic Review and Meta-Analysis.

Blocking the Programmed Cell Death Protein 1 (PD-1)/programmed death ligand-1 (PD-L1) axis has demonstrated great efficacy in cancer immunotherapy treatment and remains the central modality of immune targeting. To support the rational and tailored use of these drugs, it is important to identify reliable biomarkers related to survival. The role of the soluble form of the PD-L1 (sPD-L1) as a prognostic biomarker related to survival in solid cancer patients treated with immunotherapy has not yet been consistently evaluated.

The role of immune profile in predicting outcomes in cancer patients treated with immunotherapy.

Background: Despite the efficacy of immunotherapy, only a small percentage of patients achieves a long-term benefit in terms of overall survival. The aim of this study was to define an immune profile predicting the response to immune checkpoint inhibitors (ICIs).

Methods: Patients with advanced solid tumors, who underwent ICI treatment were enrolled in this prospective study.

Genomic and Immune Approach in Platinum Refractory HPV-Negative Head and Neck Squamous Cell Carcinoma Patients Treated with Immunotherapy: A Novel Combined Profile.

Introduction: Only a minority of patients with platinum refractory head and neck squamous cell carcinoma (PR/HNSCC) gain some lasting benefit from immunotherapy.

Methods: The combined role of the comprehensive genomic (through the FoundationOne Cdx test) and immune profiles of 10 PR/HNSCC patients treated with the anti-PD-1 nivolumab was evaluated. The immune profiles were studied both at baseline and at the second cycle of immunotherapy, weighing 20 circulating cytokines/chemokines, adhesion molecules, and 14 soluble immune checkpoints dosed through a multiplex assay.

Protection of Prisoners with Mental Health Disorders in Italy: Lights and Shadows after the Abolition of Judicial Psychiatric Hospitals.

In Italy, a person suffering from a mental disorder who commits a crime will be given a custodial security order and serve the period of admission at a (Residence for the Execution of Security Measures, hereinafter "REMS"). These institutions have been established recently and though equipped with the necessary safety measures, the focus is on psychiatric therapy. Despite being present on a national scale, access is very limited in terms of capacity.

Lacrimal Secretion Variation and Menace Response Appearance in Healthy Standardbred Foals From Birth to Four Weeks of Age.

This study assesses lacrimal secretion in healthy foals within 48 hours after birth and evaluates their variations in lacrimal secretion and menace response appearance during the first month of life. A total of 31 Standardbred foals were evaluated. Foals were housed with their dams in 4 × 4 m boxes throughout the study.

Immune effects of CDK4/6 inhibitors in patients with HR/HER2 metastatic breast cancer: Relief from immunosuppression is associated with clinical response.

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are innovative small target molecules that, in combination with endocrine therapy, have recently been employed in the treatment of patients with HR/HER2 metastatic breast cancer (mBC). In this prospective study, we investigate the impact of CDK4/6i on the immune profile of patients with HR/HER2 mBC.

Methods: Immune cell subsets were analysed using flow cytometry of peripheral blood mononuclear cells (PBMCs) isolated from patients with HR/HER2 mBC, both before and during treatment.

Circulating immune profile can predict survival of metastatic uveal melanoma patients: results of an exploratory study.

Metastatic uveal melanoma (UM) is a poor prognosis malignancy. Immunotherapy is commonly employed, despite the low activity, considering the lack of other effective systemic treatments. In this study, the prognostic and predictive role of soluble immune checkpoints and inflammatory cytokines/chemokines in 22 metastatic UM patients was evaluated.

Multiple Arbuscular Mycorrhizal Fungal Consortia Enhance Yield and Fatty Acids of : A Two-Year Field Study on Agronomic Traits and Tracing of Fungal Persistence.

Arbuscular mycorrhizal fungi are promoted as biofertilizers due to potential benefits in crop productivity, and macro- and microelement uptake. However, crop response to arbuscular mycorrhizal fungi (AMF) inoculation is context-dependent, and AMF diversity and field establishment and persistence of inoculants can greatly contribute to variation in outcomes. This study was designed to test the hypotheses that multiple and local AMF inoculants could enhance alfalfa yield and fatty acids (FA) compared to exotic isolates either single or in the mixture.