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.

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.

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.

ANMCO position paper on the management of hypercholesterolaemia in patients with acute coronary syndrome.

Patients suffering from acute coronary syndrome (ACS) present a high risk of recurrence and new adverse cardiovascular events after hospital discharge. Elevated plasma LDL-cholesterol (LDL-C) levels have been shown to be a causal factor for the development of coronary heart disease, and robust clinical evidence has documented that LDL-C levels decrease linearly correlates with a reduction in cardiovascular events. Recent studies have also demonstrated the safety and efficacy of an early and significant reduction in LDL-C levels in patients with ACS.

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.

Proteomic characterization of extracellular vesicles released by third stage larvae of the zoonotic parasite (Nematoda: Anisakidae).

Introduction: is a sibling species within the (s.l.) complex requiring marine homeothermic (mainly cetaceans) and heterothermic (crustaceans, fish, and cephalopods) organisms to complete its life cycle.

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.

[ANMCO Position paper: Management of hypercholesterolemia in patients with acute coronary syndrome].

Patients suffering from acute coronary syndromes (ACS) present a high risk of recurrence and new adverse cardiovascular events after hospital discharge. Elevated plasma LDL-cholesterol (LDL-C) levels have been shown to be a causal factor for the development of coronary heart disease, and robust clinical evidence has documented that a decrease of LDL-C levels correlates linearly with a reduction in cardiovascular events. Recent studies have also demonstrated the safety and efficacy of an early and significant reduction in LDL-C levels in patients with ACS.

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.

Glycan-Lectin Interactions as Novel Immunosuppression Drivers in Glioblastoma.

Despite diagnostic and therapeutic improvements, glioblastoma (GB) remains one of the most threatening brain tumor in adults, underlining the urgent need of new therapeutic targets. Lectins are glycan-binding proteins that regulate several biological processes through the recognition of specific sugar motifs. Lectins and their ligands are found on immune cells, endothelial cells and, also, tumor cells, pointing out a strong correlation among immunity, tumor microenvironment and vascularization.

ANMCO statement on the use of sodium-glucose cotransporter 2 inhibitors in patients with heart failure: a practical guide for a streamlined implementation.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, dapagliflozin, and empagliflozin, first developed as glucose-lowering agents for the treatment of Type 2 diabetes, have been demonstrated to improve prognosis in patients with heart failure and reduced ejection fraction (HFrEF) regardless of the presence of diabetes. Since these drugs have only recently been included among the four pillars of HFrEF treatment, cardiologists are still unfamiliar with their use in this setting. This article provides an up-to-date practical guide for the initiation and monitoring of patients treated with SGLT2 inhibitors.

[ANMCO Position paper: Antithrombotic treatment of patients with atrial fibrillation undergoing intracoronary stenting and/or acute coronary syndromes].

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with or without acute coronary syndromes (ACS) represent a subgroup with a challenging pharmacological management. Indeed, if on the one hand antithrombotic therapy should reduce the risk related to recurrent ischemic events and/or stent thrombosis, on the other hand care should be taken to avoid major bleeding events. In recent years, several trials, which overall included more than 12 000 patients, have been conducted demonstrating the safety of different therapeutic combinations of oral antiplatelet and anticoagulant agents.

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 CD137+ T Cells Correlate with Improved Response to Anti-PD1 Immunotherapy in Patients with Cancer.

Purpose: CD137 molecule is expressed by activated lymphocytes, and in patients with cancer identifies the tumor-reactive T cells. In solid tumors, high levels of circulating CD137+ T cells are associated with the clinical response and the disease-free status. Here, we examined the role of the CD137+ T cells in the improvement of patients' selection for immunotherapy treatment.

[ANMCO Position paper: Prescription appropriateness of direct oral anticoagulants for stroke and systemic thromboembolis with non-valvular atrial fibrillation].

The prescription appropriateness of direct oral anticoagulants (DOACs [dabigatran, rivaroxaban, apixaban, and edoxaban]) is carefully regulated, taking into account the criteria established in phase III trials and listed in the summary of the product characteristics of the four DOACs. In clinical practice, prescriptions are not always in compliance with established indications. In particular, the use of doses lower than those recommended in drug data sheets is relatively frequent.

Immunogenic Cell Death and Immunomodulatory Effects of Cabozantinib.

Cabozantinib (XL-184) is a multitarget tyrosine kinase inhibitor (TKI) targeting receptor tyrosine kinases (RTKs) involved in oncogenesis and angiogenesis. It is currently the standard therapy for medullary thyroid cancer (MTC), metastatic renal cell carcinoma (mRCC), and hepatocellular carcinoma (HCC). Combination of Cabozantinib with immunotherapy is now a standard treatment in metastatic renal cancer, and its efficacy is being tested in ongoing clinical trial in prostate cancer patients.

The Role of Soluble LAG3 and Soluble Immune Checkpoints Profile in Advanced Head and Neck Cancer: A Pilot Study.

Unresectable recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has a very poor prognosis. Soluble immune checkpoints (sICs) are circulating proteins that result from the alternative splicing of membrane proteins and can modulate the immune response to cancer cells. The aim of our pilot study was to determine the possible role of a comprehensive evaluation of sICs in the classification of prognosis and response to treatment in patients with advanced disease.

Metformin exerts anti-cancerogenic effects and reverses epithelial-to-mesenchymal transition trait in primary human intrahepatic cholangiocarcinoma cells.

Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with marked resistance to chemotherapeutics without therapies. The tumour microenvironment of iCCA is enriched of Cancer-Stem-Cells expressing Epithelial-to-Mesenchymal Transition (EMT) traits, being these features associated with aggressiveness and drug resistance. Treatment with the anti-diabetic drug Metformin, has been recently associated with reduced incidence of iCCA.