Longitudinal blood immune-inflammatory and radiomic profiling to decode different patterns of acquired resistance to immunotherapy in patients with NSCLC.

Purpose: To uncover the underpinnings of acquired resistance (AR) to immunotherapy (IO), we determined whether distinctive clinico-pathological, radiomic and peripheral blood (PB) immune-inflammatory features reflect oligo- and systemic (sys)-AR in advanced NSCLC patients undergoing immune checkpoints inhibitors.

Experimental Design: On 105 consecutive IO-treated advanced NSCLC, PB immunophenotypes, cytokines and CT-derived radiomic features (RFs), extracted from primary and merged metastatic lesions, were prospectively collected at baseline (T0) and first disease assessment (T1, 9-12 weeks), and their delta (Δ) variation [(T1-T0)/T0] computed. AR, defined as progression after initial response (complete/partial) or stable disease ≥ 6 months, was subdivided according to the number of new and/or progressive lesions in oligoAR (≤3) and sysAR (>3).

CD26 Is Differentially Expressed throughout the Life Cycle of Infantile Hemangiomas and Characterizes the Proliferative Phase.

Infantile hemangiomas (IHs) are benign vascular neoplasms of childhood (prevalence 5-10%) due to the abnormal proliferation of endothelial cells. IHs are characterized by a peculiar natural life cycle enclosing three phases: proliferative (≤12 months), involuting (≥13 months), and involuted (up to 4-7 years). The mechanisms underlying this neoplastic disease still remain uncovered.

Β-blockers activate autophagy on infantile hemangioma-derived endothelial cells in vitro.

Unlabelled: The mechanisms underlying the success of propranolol in the treatment of infantile hemangioma (IH) remain elusive and do not fully explain the rapid regression of hemangiomatous lesions following drug administration. As autophagy is critically implicated in vascular homeostasis, we determined whether β-blockers trigger the autophagic flux on infantile hemangioma-derived endothelial cells (Hem-ECs) in vitro.

Material And Methods: Fresh tissue specimens, surgically removed for therapeutic purpose to seven children affected by proliferative IH, were subjected to enzymatic digestion.

Integrated MRI-Immune-Genomic Features Enclose a Risk Stratification Model in Patients Affected by Glioblastoma.

Background: The aim of the present study was to dissect the clinical outcome of GB patients through the integration of molecular, immunophenotypic and MR imaging features.

Methods: We enrolled 57 histologically proven and molecularly tested GB patients (5.3% IDH-1 mutant).

Validation of a radiomic approach to decipher NSCLC immune microenvironment in surgically resected patients.

Radiomics has emerged as a noninvasive tool endowed with the potential to intercept tumor characteristics thereby predicting clinical outcome. In a recent study on resected non-small cell lung cancer (NSCLC), we identified highly prognostic computed tomography (CT) -derived radiomic features (RFs), which in turn were able to discriminate hot from cold tumor immune microenvironment (TIME). We aimed at validating a radiomic model capable of dissecting specific TIME profiles bearing prognostic power in resected NSCLC.

Short-term effects on emergency room access or hospital admissions for cardio-respiratory diseases: methodology and results after three years of functioning of a waste-to-energy incinerator in Turin (Italy).

This study is part of the health surveillance system set up with the construction of a waste-to-energy (WTE) plant in Turin (Italy). Circulatory and respiratory diseases in emergency room (ER) accesses and first hospital admissions were considered. Main concerns of population living in the area near WTE were to know whether single and repeated peaks in emissions would correspond to adverse health effects.

Dataset on the identification of a prognostic radio-immune signature in surgically resected Non Small Cell Lung Cancer.

The immune regulation of cancer growth and regression has been underscored by the recent success of immunotherapy. The possibility that immune microenvironmental factors may impact on clinical outcome and treatment response still requires intense investigations. Hereby, supporting data of the research article "Integrated CT Imaging and Tissue Immune Features Disclose a Radio-Immune Signature with High Prognostic Impact on Surgically Resected NSCLC" [1], are presented.

Integrated CT imaging and tissue immune features disclose a radio-immune signature with high prognostic impact on surgically resected NSCLC.

Objectives: Qualitative and quantitative CT imaging features might intercept the multifaceted tumor immune microenvironment (TIME), providing a non-invasive approach to design new prognostic models in NSCLC patients.

Materials And Methods: Our study population consisted of 100 surgically resected NSCLC patients among which 31 served as a validation cohort for quantitative image analysis. TIME was classified according to PD-L1 expression and the magnitude of Tumor Infiltrating Lymphocytes (TILs) and further defined as hot or cold by the tissue analysis of effector (CD8-to-CD3/PD-1-to-CD8) or inert (CD8-to-CD3/PD-1-to-CD8) phenotypes.

Blood and lymphatic vessels contribute to the impact of the immune microenvironment on clinical outcome in non-small-cell lung cancer.

Objectives: Lymphangiogenesis plays a critical role in the immune response, tumour progression and therapy effectiveness. The aim of this study was to determine whether the interplay between the lymphatic and the blood microvasculature, tumour-infiltrating lymphocytes and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint constitutes an immune microenvironment affecting the clinical outcome of patients with non-small-cell lung cancer.

Methods: Samples from 50 squamous cell carcinomas and 42 adenocarcinomas were subjected to immunofluorescence to detect blood and lymphatic vessels.

Low PD-1 Expression in Cytotoxic CD8 Tumor-Infiltrating Lymphocytes Confers an Immune-Privileged Tissue Microenvironment in NSCLC with a Prognostic and Predictive Value.

The success of immune checkpoint inhibitors strengthens the notion that tumor growth and regression are immune regulated. To determine whether distinct tissue immune microenvironments differentially affect clinical outcome in non-small cell lung cancer (NSCLC), an extended analysis of PD-L1 and tumor-infiltrating lymphocytes (TIL) was performed. Samples from resected adenocarcinoma (ADC 42), squamous cell carcinoma (SCC 58), and 26 advanced diseases (13 ADC and 13 SCC) treated with nivolumab were analyzed.

Sensory neuropathy hampers nociception-mediated bone marrow stem cell release in mice and patients with diabetes.

Aims/hypothesis: Upon tissue injury, peripheral sensory neurons release nociceptive factors (e.g. substance P [SP]), which exert local and systemic actions including the recruitment of bone marrow (BM)-derived haematopoietic stem and progenitor cells (HSPCs) endowed with paracrine pro-angiogenic properties.

Isolation and Characterization of Human Lung Lymphatic Endothelial Cells.

Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied.

Cardioprotection by Targeting the Pool of Resident and Extracardiac Progenitors.

The adult heart has the capacity to generate new myocytes that are markedly enhanced in acute and chronic heart failure of ischemic and non-ischemic origin. In addition, a pool of blood trafficking progenitor cells able to sense myocardial damage may home to the sites of injury participating to cardiac repair. This new view of myocardial biology leads to an expanding long-term research and therapeutic goals for cardioprotection.

Lung mesenchymal cells function as an inductive microenvironment for human lung cancer propagating cells†.

Objectives: The aim of the present study was to characterize the biological properties and in vivo tumourigenic potential of mesenchymal cells (MCs) obtained from non-small-cell lung cancer (NSCLC) samples.

Methods: NSCLC samples (53 adenocarcinomas and 24 squamous-cell carcinomas) surgically removed from 46 males and 31 females were processed to identify mesenchymal cells from human lung cancer (hLc-MCs). hLc-MCs were separated from neoplastic epithelial cells, expanded and extensively characterized in vitro.

Anti-inflammatory effect of 3,4-DHPEA-EDA [2-(3,4 -hydroxyphenyl) ethyl (3S, 4E)-4-formyl-3-(2-oxoethyl)hex-4-enoate] on primary human vascular endothelial cells.

Diets in which fat is significantly provided by olive oil and are relatively rich in vegetables, have been associated with a low incidence of cardiovascular diseases, mostly due to the presence of several phenolic compounds which have anti-oxidant and antiinflammatory properties. [1]. In this work, we describe the anti-inflammatory effect of 3,4-DHPEA-EDA in a cell model that we developed to mimic inflammatory injury of endothelium.

Human cytomegalovirus productively infects lymphatic endothelial cells and induces a secretome that promotes angiogenesis and lymphangiogenesis through interleukin-6 and granulocyte-macrophage colony-stimulating factor.

Endothelial cells (ECs) are a site of human cytomegalovirus (HCMV) productive replication, haematogenous dissemination and persistence, and are assumed to play a critical role in the development of HCMV-associated vascular diseases. Although early reports have shown the presence of HCMV antigens and DNA in lymphoid tissues, the ability of HCMV to infect lymphatic ECs (LECs) has remained unaddressed due to the lack of a suitable in vitro system. This study provided evidence that a clinical isolate of HCMV (retaining its natural endotheliotropism) was able to productively infect purified lymph node-derived LECs and that it dysregulated the expression of several LEC genes involved in the inflammatory response to viral infection.

Insulin lispro protamine suspension in intensive insulin treatment: an Italian observational study.

Objective: This observational study examined the effects of insulin lispro protamine suspension (ILPS) given as basal insulin in intensive insulin regimens in patients with type 1 and type 2 diabetes mellitus who attended a reference outpatient centre for the treatment of diabetes due to poor glycaemic control, frequent hypoglycaemia or intolerance to previous therapy.

Methods: The study population included 64 patients, 33 male and 31 female, mean age 59.6 years; 50 patients were receiving an insulin regimen, while 14 had previously been treated with oral antidiabetic drugs (OADs).

Isolation, purification, and heterogeneity of human lymphatic endothelial cells from different tissues.

Relatively few attempts have been made in the past to isolate and expand lymphatic endothelial cells (LECs). Recently this task has become feasible thanks to the identification of new lymphatic markers such as Podoplanin, Lyve-1, Prox-1 and D2-40. Using a two-step purification method based on the sorting of endothelial cells with Ulex Europaeus Agglutinin 1-coated beads followed by purification with monoclonal antibody D2-40, we were able to purify and in vitro expand human derived LECs from tissues such as lymph node, spleen, thymus, palatine tonsil and iliac lymphatic vessels.