The advent of immune stimulating CAFs in cancer.

The theory that cancer-associated fibroblasts (CAFs) are immunosuppressive cells has prevailed throughout the past decade. However, recent high-throughput, high-resolution mesenchyme-directed single-cell studies have harnessed computational advances to functionally characterize cell states, highlighting the existence of immunostimulatory CAFs. Our group and others have uncovered and experimentally substantiated key functions of cancer antigen-presenting CAFs in T cell immunity, both in vitro and in vivo, refuting the conventional assumption that CAFs impede adaptive immune rejection of tumours.

Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts.

A key unknown of the functional space in tumor immunity is whether CD4 T cells depend on intratumoral MHCII cancer antigen recognition. MHCII-expressing, antigen-presenting cancer-associated fibroblasts (apCAFs) have been found in breast and pancreatic tumors and are considered to be immunosuppressive. This analysis shows that antigen-presenting fibroblasts are frequent in human lung non-small cell carcinomas, where they seem to actively promote rather than suppress MHCII immunity.

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition).

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells.

Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma.

Lung adenocarcinoma (LUAD)-derived Wnts increase cancer cell proliferative/stemness potential, but whether they impact the immune microenvironment is unknown. Here we show that LUAD cells use paracrine Wnt1 signaling to induce immune resistance. In TCGA, Wnt1 correlates strongly with tolerogenic genes.

Cigarette Smoke-Induced Emphysema Exhausts Early Cytotoxic CD8 T Cell Responses against Nascent Lung Cancer Cells.

Chronic obstructive pulmonary disease is a chronic inflammatory disorder with an increased incidence of lung cancer. The emphysema component of chronic obstructive pulmonary disease confers the greatest proportion to lung cancer risk. Although tumors create inflammatory conditions to escape immunity, the immunological responses that control growth of nascent cancer cells in pre-established inflammatory microenvironments are unknown.

Tolerogenic signaling by pulmonary CD1c+ dendritic cells induces regulatory T cells in patients with chronic obstructive pulmonary disease by IL-27/IL-10/inducible costimulator ligand.

Background: Increased mortality rates in patients with chronic obstructive pulmonary disease (COPD) are largely due to severe infectious exacerbations. Impaired respiratory immunity is linked to the enhanced susceptibility to infections. Dendritic cells (DCs) direct host immune responses toward immunity or tolerance.

CXCL13 production in B cells via Toll-like receptor/lymphotoxin receptor signaling is involved in lymphoid neogenesis in chronic obstructive pulmonary disease.

Rationale: Little is known about what drives the appearance of lymphoid follicles (LFs), which may function as lymphoid organs in chronic obstructive pulmonary disease (COPD). In animal infection models, pulmonary LF formation requires expression of homeostatic chemokines by stromal cells and dendritic cells, partly via lymphotoxin.

Objectives: To study the role of homeostatic chemokines in LF formation in COPD and to identify mechanism(s) responsible for their production.

Sputum and nasal lavage lung-specific biomarkers before and after smoking cessation.

Background: Little is known about the effect of smoking cessation on airway inflammation. Secretory Leukocyte Protease Inhibitor (SLPI), Clara Cell protein 16 (CC16), elafin and human defensin beta-2 (HBD-2) protect human airways against inflammation and oxidative stress. In this longitudinal study we aimed to investigate changes in sputum and nasal lavage SLPI, CC16, elafin and HBD-2 levels in healthy smokers after 6 and 12 months of smoking cessation.

Innate immunity proteins in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.

Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) may be caused by epithelial cell injury. Epithelial cells respond to injury by secreting innate immunity proteins. To investigate whether altered levels of innate immunity proteins are observed in COPD and IPF, the authors assessed secretory leukocyte protease inhibitor (SLPI), elafin, CC16, and beta-defensin-2 levels by enzyme-linked immunosorbent assay (ELISA) in sputum supernatants from COPD patients (n = 19), smokers without COPD (n = 21), and never-smokers (n = 10) and in BALF supernatants from patients with IPF (n = 11) and subjects without IPF (n = 11).

Maintained smoking cessation for 6 months equilibrates the percentage of sputum CD8+ lymphocyte cells with that of nonsmokers.

Little is known about the longitudinal effects of smoking cessation on sputum inflammatory cells. We aimed to investigate the changes in sputum inflammatory cells and T-lymphocyte subpopulations after 6 and 12 months smoking cessation. Induced sputum was obtained from 68 healthy smokers before and after 6 months (n = 21) and 1 year (n = 14) smoking cessation and from ten healthy never-smokers.

Decreased sputum mature dendritic cells in healthy smokers and patients with chronic obstructive pulmonary disease.

Background: Asthmatics who smoke have decreased pulmonary mature dendritic cells (DCs). Chronic obstructive pulmonary disease (COPD) patients have an increased amount of pulmonary immature DCs. We hypothesized that healthy smokers and patients with COPD have decreased pulmonary mature DCs.

Decreased small airway and alveolar CD83+ dendritic cells in COPD.

Background: Dendritic cells (DCs) have been reported to be increased in the small airways of patients with COPD, but the maturity status of these cells is unclear. We have quantified the numbers of cells expressing markers associated with DC maturation.

Methods: Lung tissue was obtained at resection for lung cancer from 41 patients with COPD (30 current smokers and 11 ex-smokers; 32 steroid-treated patients and 9 steroid-naïve patients), 19 ex-smokers without COPD and 9 never-smokers without COPD.

Expression of blood dendritic cell antigens (BDCAs) by CD1a+ human pulmonary cells.

Background: Myeloid and plasmacytoid dendritic cell (DC) subsets have been recently identified in the human lung based on their differential expression of Blood DC Antigens 1-3 (BDCAs). We investigated the expression of these antigens by isolated human pulmonary CD1a(+) DCs, namely Langerhan's cells.

Methods: Using an in vitro cell culture system we successfully isolated a population of relatively pure (>70%) CD1a(+) cells from human lung tissue (n=5 subject samples) and stained these with antibodies against the myeloid DC markers BDCA1 (CD1c) and BDCA3 (CD303), the plasmacytoid DC marker BDCA2 (CD141), the Langerhan's cell marker Langerin and the maturation marker CD83.

Dendritic cells in chronic obstructive pulmonary disease: new players in an old game.

Dendritic cells (DCs) are professional antigen-presenting cells responsible for immune homeostasis. In the lung's responses to tissue damage or infection, they initiate and orchestrate innate and adaptive immunity. There are immature and mature states and at least three phenotypic and functional subsets.

Cigarette smoking alters bronchial mucosal immunity in asthma.

Rationale: Cigarette smoking worsens asthma and is associated with reduced response to corticosteroid therapy. As cigarette smoke is known to have immunomodulatory effects, we hypothesized that one mechanism by which smoking mediates its adverse effect is by reduction of the numbers of bronchial mucosal dendritic cells (DCs), which control B-cell growth and T-cell responses.

Objectives: We set out to sample the bronchial mucosa in smoking and never-smoking patients with asthma and to count DCs, B cells, and cells expressing genes for two key T-lymphocyte regulatory cytokines.

Novel insights into the aetiology and pathophysiology of increased airway inflammation during COPD exacerbations.

Airway inflammation increases during acute exacerbations of COPD. Extrinsic factors, such as airway infections, increased air pollution, and intrinsic factors, such as increased oxidative stress and altered immunity may contribute to this increase. The evidence for this and the potential mechanisms by which various aetiological agents increase inflammation during COPD exacerbations is reviewed.

Airway inflammation and cellular stress in noneosinophilic atopic asthma.

Study Objectives: It has been suggested that patients with noneosinophilic asthma (NEA) show increased numbers of sputum neutrophils and a lack of response to therapy with corticosteroids, which are features that are commonly related to COPD. The aim of our study was to test the hypothesis that airway inflammation in NEA patients is different from that seen in patients with eosinophilic asthma (EA) and is similar to COPD.

Design: Sputum cellular stress markers and neutrophilic and eosinophilic fluid-phase mediators were analyzed in asthma and COPD patients.

Isolation of myeloid and plasmacytoid dendritic cells from human bronchoalveolar lavage fluid.

Studies of bronchoalveolar lavage fluid (BALF) dendritic cells (DC) have been hampered by the scarcity of DC and the lack of DC-specific surface markers. Four surface Ag have been recently described as specific markers for distinct subsets of DC and have been used for the isolation and characterization of fresh noncultured DC from lung resection specimens: BDCA-1 (CD1c) and BDCA-3 for myeloid DC type 1 and type 2, respectively, and BDCA-2 and BDCA-4 for plasmacytoid DC. The aim of this study was to develop a new method for the isolation of BALF DC, using immunomagnetic separation of BDCA+ cells.

A prospective analysis of 184 hemoptysis cases: diagnostic impact of chest X-ray, computed tomography, bronchoscopy.

Background: The clinical presentation of hemoptysis often raises a number of diagnostic possibilities.

Objectives: This study was designed to evaluate the relative frequency of different causes of hemoptysis and the value of chest radiography, computed tomography (CT) scanning and fiber-optic bronchoscopy in the evaluation of a Greek cohort population.

Methods: We prospectively followed a total of 184 consecutive patients (137 males/47 females, 145 smokers/39 nonsmokers) admitted with hemoptysis between January 2001 and December 2003 to the University Hospital of Heraklion.

Comparison of induced sputum inflammatory profiles between childhood and adult-onset asthma.

The aim of this study was to investigate differences in airway inflammation between childhood and adult-onset asthma. A total of 47 asthmatic subjects were recruited from patients attending outpatient clinic. A group of 32 adults, mean age 42.

Laboratory markers for COPD in "susceptible" smokers.

Smoking is the major risk factor for the development of chronic obstructive pulmonary disease. Apart from the important preventive steps of smoking cessation, there are no other specific treatments for COPD that are as effective in reversing the condition. However, only a relatively small proportion of smokers-about 15%-will develop clinically relevant COPD.