1,720,997 research outputs found
The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion
Full text linkSuppression of antitumor immune responses is one of the main mechanisms by which tumor cells escape from destruction by the immune system. Myeloid-derived suppressor cells (MDSCs) represent the main immunosuppressive cells present in the tumor microenvironment (TME) that sustain cancer progression. MDSCs are a heterogeneous group of immature myeloid cells with a potent activity against T-cell. Studies in mice have demonstrated that MDSCs accumulate in several types of cancer where they promote invasion, angiogenesis, and metastasis formation and inhibit antitumor immunity. In addition, different clinical studies have shown that MDSCs levels in the peripheral blood of cancer patients correlates with tumor burden, stage and with poor prognosis in multiple malignancies. Thus, MDSCs are the major obstacle to many cancer immunotherapies and their targeting may be a beneficial strategy for improvement the efficiency of immunotherapeutic interventions. However, the great heterogeneity of these cells makes their identification in human cancer very challenging. Since both the phenotype and mechanisms of action of MDSCs appear to be tumor-dependent, it is important to accurately characterized the precise MDSC subsets that have clinical relevance in each tumor environment to more efficiently target them. In this review we summarize the phenotype and the suppressive mechanisms of MDSCs populations expanded within different tumor contexts. Further, we discuss about their clinical relevance for cancer diagnosis and therapy
New drugs from the sea: Pro-apoptotic activity of sponges and algae derived compounds
No full textNatural compounds derived from marine organisms exhibit a wide variety of biological activities. Over the last decades, a great interest has been focused on the anti-tumour role of sponges and algae that constitute the major source of these bioactive metabolites. A substantial number of chemically different structures from different species have demonstrated inhibition of tumour growth and progression by inducing apoptosis in several types of human cancer. The molecular mechanisms by which marine natural products activate apoptosis mainly include (1) a dysregulation of the mitochondrial pathway; (2) the activation of caspases; and/or (3) increase of death signals through transmembrane death receptors. This great variety of mechanisms of action may help to overcome the multitude of resistances exhibited by different tumour specimens. Therefore, products from marine organisms and their synthetic derivates might represent promising sources for new anticancer drugs, both as single agents or as co-adjuvants with other chemotherapeutics. This review will focus on some selected bioactive molecules from sponges and algae with pro-apoptotic potential in tumour cells
IL-9R loss in innate lymphoid cell type 2 (ILC2) reflects Treg impairment in mastocytosis patients
No full textHealthy and Patient Type 2 Innate Lymphoid Cells are Differently Affected by in vitro Culture Conditions
Full text linkMaryline Falquet,1,2 Giuseppe Ercolano,1,2 Peter Jandus,3 Camilla Jandus,1,2,* Sara Trabanelli1,2,* 1Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland; 2Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; 3Division of Immunology and Allergology, University Hospital and Medical Faculty, Geneva, Switzerland*These authors contributed equally to this workCorrespondence: Sara TrabanelliDepartment of Pathology and Immunology, University of Geneva, 1211, Rue Michel-Servet 1, Geneva 4, CH-1211, SwitzerlandEmail [email protected]: Type 2 innate lymphoid cells (ILC2s) have emerged as key players in the development of type 2 driven diseases such as allergy and asthma. Due to their low number in the circulation, in vitro expansion is needed to unravel their mechanisms of action.Purpose: The aim of this study is to assess the impact of different culture conditions and address whether the method of expansion may distinctly affect healthy donor or patient-derived ILC2s.Methods: Here, we described the impact of six different culture conditions on the proliferation, phenotype and function of human ILC2s freshly obtained from healthy donors (healthy ILC2s) and allergic patients (patient ILC2s).Results: We showed that the cytokine cocktail or the PHA induced the highest proliferation of healthy ILC2s and patient ILC2s, respectively. We observed that the stromal cells OP9, used as ILC2 feeders, did not boost their proliferation, but impaired the activation marker expression and the function of patient ILC2s. Furthermore, we demonstrated that the culture conditions differently impacted the activation state of c-Kithigh and c-Kitlow ILC2s, in both healthy donors and allergic patients. Last, we also observed that ILC2s expanded only with IL-2 and IL-7 were the most prone to secrete IL-5 and IL-13 upon IL-33 stimulation. In contrast, in patients, the addition of OP9 cells during the expansion restrained their type 2 cytokine secretory functions.Conclusion: This report highlights that culture conditions distinctly impacted on the healthy or patient ILC2 behavior, with important consequences for their study in disease settings.Keywords: type 2 innate lymphoid cells, in vitro expansion, allergic patients, cytokine
ILC2s: New Actors in Tumor Immunity
Full text linkInnate lymphoid cells (ILCs) represent the most recently identified family of innate lymphocytes that act as first responders, maintaining tissue homeostasis and protecting epithelial barriers. In the last few years, group 2 ILCs (ILC2s) have emerged as key regulators in several immunological processes such as asthma and allergy. Whilst ILC2s are currently being evaluated as novel targets for immunotherapy in these diseases, their involvement in tumor immunity has only recently begun to be deciphered. Here, we provide a comprehensive overview of the pleiotropic roles of ILC2s in different tumor settings. Furthermore, we discuss how different therapeutic approaches targeting ILC2s could improve the efficacy of current tumor immunotherapies
Olive leaf extract inhibits metastatic melanoma spread through suppression of epithelial to mesenchymal transition
Full text linkOlive tree leaves are an abundant source of bioactive compounds with several beneficial effects for human health, including a protective role against many types of cancer. In this study, we investigated the effect of an extract, obtained from olive tree (Olea europaea L.) leaves (OLE), on proliferation, invasion, and epithelial to mesenchymal transition (EMT) on metastatic melanoma, the highly aggressive form of skin cancer and the deadliest diseases. Our results demonstrated that OLE inhibited melanoma cells proliferation through cell cycle arrest and induction of apoptotic cell death. Moreover, OLE suppressed the migration, invasion, and colonies formation of human melanoma cells. Similar to our in vitro findings, we demonstrated that the oral administration of OLE inhibited cutaneous tumor growth and lung metastasis formation in vivo by modulating the expression of EMT related factors. In addition, the anti-proliferative and anti-invasive effects of OLE against melanoma were also related to a simultaneous targeting of mitogen-activated protein kinase and PI3K pathways, both in vitro and in vivo. In conclusion, our findings suggest that OLE has the potential to inhibit the metastatic spread of melanoma cells thanks to its multifaceted mechanistic effects, and may represent a new add-on therapy for the management of metastatic melanoma
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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