News Beyond Our Pages
Authors: Marc E. Rothenberg, Jean Bousquet
Journal: Journal of Allergy and Clinical Immunology (2015)

Approximately half of asthmatic patients, regardless of disease severity, exhibit a TH2 molecular endotype. The expression and production of the TH2 cytokines IL-4, IL-5, and IL-13 have been shown in isolated cell systems and invertebrates to be controlled by the zinc finger transcription factor GATA-3, which is essential for TH2 cell differentiation and activation and considered to be the master transcription factor of the TH2 pathway. Thus therapeutic targeting of GATA-3 might be beneficial, which led Krug et al (http://dx.doi.org/10.1056/NEJMoa1411776) to evaluate the safety and efficacy of SB010, a novel DNA enzyme that is able to cleave and inactivate GATA-3 mRNA. The authors discovered that treatment with inhaled SB010 significantly attenuated both late and early asthmatic responses after allergen provocation in patients with allergic asthma. Moreover, biomarker analysis showed an attenuation of TH2-regulated inflammatory responses. This is an exciting development with a new therapeutic class of agents, and further clinical studies are warranted to determine whether there are clinical benefits in patients who have symptomatic and persistent asthma with a predominant TH2 phenotype.Significantly attenuated both late and early asthmatic responses after allergen provocationHarald RenzView Large Image Figure ViewerDownload Hi-res image Download (PPT) Significantly attenuated both late and early asthmatic responses after allergen provocation We asked author Harald Renz, MD, from Philipps University Marburg to comment on the significance of these results: “This is the first time the transcription factor has been successfully targeted in asthmatic patients. It is also the first time that a new class of drugs, called DNAzymes, has been successfully and safely administered by inhalation.’’ The activation and maintenance of eosinophils is dependent on the presence of IL-5, suggesting that the reduction of IL-5–mediated signaling could therefore disrupt the maturation and survival of eosinophils. Here, Castro et al (Lancet Respir Med 2015;3:355-66) aimed to assess the efficacy and safety of reslizumab, a humanized IgG4k anti–IL-5 mAb that disrupts eosinophil maturation and promotes programmed cell death in patients with inadequately controlled moderate-to-severe asthma with high eosinophil counts. The authors observed a reduction in asthma exacerbations and improvement in multiple measures of asthma control. Their results support the use of reslizumab as a targeted treatment op tion for patients with inadequately controlled asthma and increased blood eosinophil counts who did not respond to an inhaled corticosteroid–based treatment.Targeted treatment option for patients with inadequately controlled asthma and increased blood eosinophil countsMario CastroView Large Image Figure ViewerDownload Hi-res image Download (PPT) Targeted treatment option for patients with inadequately controlled asthma and increased blood eosinophil counts We asked author Mario Castro, MD, from Washington University School of Medicine to comment on the significance of these results: “Data from two replicate, double-blind, placebo-controlled global studies showed that in patients with asthma and elevated blood eosinophils who were inadequately controlled on an ICS-based regimen, reslizumab significantly reduced the annual rate of clinical asthma exacerbations, and provided sustained improvements in lung function, asthma symptoms, and asthma-related quality of life. We are excited by our results that demonstrate targeted eosinophil phenotype therapy in patients with severe asthma identified by a simple blood test really works.’’ Tumor-associated eosinophilia is frequently observed in patients with cancer; however, despite numerous studies of such patients, as well as mouse models of cancer, it has remained uncertain whether eosinophils contribute to tumor immunity or are mere bystander cells. Carretero et al (Nat Immunol 2015, http://dx.doi.org/10.1038/ni.3159) report that activated eosinophils are essential for tumor rejection in the presence of tumor-specific CD8+ T cells. The authors show that tumor-homing eosinophils secrete chemoattractants that guide T cells into the tumor, which results in tumor eradication and survival. In fact, activated eosinophils initiated substantial changes in the tumor microenvironment, including macrophage polarization and normalization of the tumor vasculature, which are known to promote tumor rejection. This study presents a new concept that eosinophils might emerge as a promising tool for the improvement of clinical cancer immunotherapy. (Image licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Carcinoma_planoepitheliale_keratodes_laryngis.jpg#/media/File:Carcinoma_planoepitheliale_keratodes_laryngis.jpg.)Eosinophils might emerge as a promising tool for the improvement of clinical cancer immunotherapyGünter J. HämmerlingView Large Image Figure ViewerDownload Hi-res image Download (PPT) Eosinophils might emerge as a promising tool for the improvement of clinical cancer immunotherapy We asked author Günter J. Hämmerling, PhD, from the German Cancer Research Center to comment on the significance of these results: “Our study shows that eosinophils by themselves are not very effective against tumors. Instead, they act as powerful accessory cells which modify the tumor microenvironment and attract cytotoxic T cells into the tumor, so that efficient tumor rejection is obtained. These results provide a new concept for eosinophils in cancer immunity and pave the way for novel therapeutic strategies.’’ The relatively sparse but diverse microbiome in human lungs might become less diverse in patients with chronic obstructive pulmonary disease (COPD). Although the pathogenesis of small airways obstruction and the emphysematous destruction responsible for progressive airflow limitation in patients with COPD has been associated with the host innate and adaptive inflammatory immune response, the antigens that drive this response remain poorly understood. Here, Sze et al (Am J Respir Crit Care Med 2015, http://dx.doi.org/10.1164/rccm.201502-0223OC) used culture-independent pyrosequencing microbiome analysis and compared the lung tissue of patients with COPD with healthy tissue. The authors observed a decrease in microbial diversity that was associated with emphysematous destruction, remodeling of the bronchiolar and alveolar tissue, and infiltration of the tissue by CD4+ T cells. Moreover, expression profiles of 859 and 235 genes were associated with either enrichment or reductions of Firmicutes and Proteobacteria, respectively. These results support the hypothesis that there is a host immune response to microorganisms within the lung microbiome that appears to contribute to the pathogenesis of COPD.A host immune response to microorganisms within the lung microbiomeNews items were written by medical writer Kristina Bielewicz, MS.Find more News Beyond Our Pages online at www.jaci-nbop.blogspot.com. A host immune response to microorganisms within the lung microbiome News items were written by medical writer Kristina Bielewicz, MS. Find more News Beyond Our Pages online at www.jaci-nbop.blogspot.com.