Polymorphonuclear Myeloid-Derived Suppressor Cells Are Abundant in Peripheral Blood of Cancer Patients and Suppress Natural Killer Cell Anti-Tumor Activity.

Tumor microenvironment (TME) includes a wide variety of cell types and soluble factors capable of suppressing immune-responses. While the role of NK cells in TME has been analyzed, limited information is available on the presence and the effect of polymorphonuclear (PMN) myeloid-derived suppressor cells, (MDSC). Among the immunomodulatory cells present in TME, MDSC are potentially efficient in counteracting the anti-tumor activity of several effector cells.

IL-27 Mediates PD-L1 Expression and Release by Human Mesothelioma Cells.

Malignant mesothelioma (MM) is a rare tumor with an unfavorable prognosis. MM genesis involves asbestos-mediated local inflammation, supported by several cytokines, including IL-6. Recent data showed that targeting PD-1/PD-L1 is an effective therapy in MM.

Effectiveness and Safety of Immune Checkpoint Inhibitors for Patients with Advanced Non Small-Cell Lung Cancer in Real-World: Review and Meta-Analysis.

Immunotherapy based on anti PD-1/PD-L1 inhibitors is the new standard of advanced non-small cell lung cancers. Pembrolizumab, nivolumab and atezolizumab are used in clinical practice. The strict eligibility criteria of clinical trials do not allow researchers to fully represent treatment effects in the patients that will ultimately use these drugs.

Glucocorticoids and the cytokines IL-12, IL-15, and IL-18 present in the tumor microenvironment induce PD-1 expression on human natural killer cells.

Background: Programmed cell death protein 1 (PD-1)-immune checkpoint blockade has provided significant clinical efficacy across various types of cancer by unleashing both T and natural killer (NK) cell-mediated antitumor responses. However, resistance to immunotherapy occurs for many patients, rendering the identification of the mechanisms that control PD-1 expression extremely important to increase the response to the therapy.

Objective: We sought to identify the stimuli and the molecular mechanisms that induce the de novo PD-1 expression on human NK cells in the tumor setting.

Presence of innate lymphoid cells in pleural effusions of primary and metastatic tumors: Functional analysis and expression of PD-1 receptor.

The tumor microenvironment (TM) contains a wide variety of cell types and soluble factors capable of suppressing immune responses. While the presence of NK cells in pleural effusions (PE) has been documented, no information exists on the presence of other innate lymphoid cell (ILC) subsets and on the expression of programmed cell death-1 (PD-1) in NK and ILC. The presence of ILC was assessed in PE of 54 patients (n = 33 with mesothelioma, n = 15 with adenocarcinoma and n = 6 with inflammatory pleural diseases) by cell staining with suitable antibody combinations and cytofluorimetric analysis.

PD-1 in human NK cells: evidence of cytoplasmic mRNA and protein expression.

Under physiological conditions, PD-1/PD-L1 interactions regulate unwanted over-reactions of immune cells and contribute to maintain peripheral tolerance. However, in tumor microenvironment, this interaction may greatly compromise the immune-mediated anti-tumor activity. PD-1 NK cells have been detected in high percentage in peripheral blood and ascitic fluid of ovarian carcinoma patients.

GPR56 as a novel marker identifying the CD56dull CD16+ NK cell subset both in blood stream and in inflamed peripheral tissues.

To define novel human NK cell markers, we generated two mAbs specific for G-protein-coupled receptor 56 (GPR56), a surface glycoprotein that appears to be involved in cell-to-cell and cell-to-matrix interactions. GPR56 has been described in selected normal tissues, and in certain tumors, while, as yet, its expression on leukocytes is unknown. In this study, we show that anti-GPR56 mAbs, among leukocytes, prevalently recognize NK cells.

Melanoma-associated fibroblasts modulate NK cell phenotype and antitumor cytotoxicity.

Although the role of the tumor microenvironment in the process of cancer progression has been extensively investigated, the contribution of different stromal components to tumor growth and/or evasion from immune surveillance is still only partially defined. In this study we analyzed fibroblasts derived from metastatic melanomas and provide evidence for their strong immunosuppressive activity. In coculture experiments, melanoma-derived fibroblasts sharply interfered with NK cell functions including cytotoxicity and cytokine production.

Levocetirizine in the treatment of allergic diseases.

Background: Levocetirizine, the R-enantiomer of cetirizine dihydrochloride, is a new molecule with a potent and selective antihistamine activity.

Objective: To investigate the evidence that levocetirizine is an effective therapy for allergic disease.

Methods: Evaluation of published articles in English, or having an English abstract.

Analysis of NK cell/DC interaction in NK-type lymphoproliferative disease of granular lymphocytes (LDGL): role of DNAM-1 and NKp30.

Objective: Natural killer (NK) cells and dendritic cells (DC) can give rise to reciprocal functional interactions resulting in promotion of DC maturation, killing of immature DC (iDC), and proliferation of NK cells. In this study, we analyze whether, in NK-lymphoproliferative disease of granular lymphocytes (LDGL) patients, this function could be altered and contribute to the persistence of the disease.

Materials And Methods: Freshly isolated peripheral blood NK granular lymphocytes (GL) and NK cell lines derived from 13 different NK-LDGL patients were analyzed in coculture experiments to evaluate their ability to interact with monocyte-derived DCs (Mo-DC).

New insights into airway remodelling in asthma and its possible modulation.

Purpose Of Review: Airway remodelling, a central feature of asthma, is characterized by an alteration in the size, mass or number of tissue components which occur in and around the trachea, bronchi and bronchioles in the airways in response to injury and/or inflammation. The present review focuses on the most recent literature on airway remodelling and on the different drugs commonly used or potentially useful in the treatment of asthma with a particular attention to the studies conducted by our group in the last few years.

Recent Findings: The interaction between the epithelium and mesenchymal elements such as fibroblasts is essential for normal airway repair.

Perturbations of natural killer cell regulatory functions in respiratory allergic diseases.

Background: Allergic diseases are characterized by abnormal responses to allergens favored by an inappropriate regulation of the T(H)1-T(H)2 polarization. Natural killer (NK) cells give rise to a complex NK/dendritic cell (DC) cross-talk that would help T(H)1 responses.

Objective: By analyzing peripheral blood NK cells from 12 patients with either allergic rhinitis or rhinitis and intermittent asthma, we evaluated whether these cells were impaired in their ability to interact with DCs.

Importance of fibroblasts-myofibroblasts in asthma-induced airway remodeling.

Asthma is a chronic airway disorder principally characterized by bronchial hyperreactivity and airflow obstruction. Increased epithelial and smooth muscle thickness, goblet cell hyperplasia, increased mucus secretion, abnormal deposition of extracellular matrix (ECM) components in the basement membrane (BM) layer and angiogenesis are all events which occur in asthma and are defined with the general term of remodeling. This is an important feature whose repetition and regeneration may bring to an abnormal or exaggerated response to airway insults.