1,721,031 research outputs found
Immune receptor CD137 as a biomarker in solid tumors and potential immunotherapeutic target in glioblastoma
No full textBackground: Glioblastoma (GBM) is one of the most threatening tumors in adults. GBM treatment faces challenges in enhancing patient survival and expanding therapeutic possibilities, especially considering the compromised state of the immune system in this "immunologically privileged" tumor. Understanding the unique immune dynamics within GBM is crucial for tailoring effective therapies.
Aim: The objective of this study is to investigate the role of the immune co-receptor CD137 as biomarker of response to immunotherapy in patients with solid tumors and elucidate its potential role as a biomarker and therapeutic target in GBM.
The research investigates the expression of CD137 within distinct circulating T cell subsets in various solid tumors in human patients treated with anti-PD1 agents to identify and validate its role as immune biomarker. Moreover, the research investigates the expression of CD137 in different T-cell subsets within the GBM microenvironment, exploring the complex relationship among CD137, T-cell exhaustion, immunosuppression, and immunotherapy responsiveness. Lastly, these findings may be translated into a novel therapeutic approach to improve the immune response against GBM.
Results: Through investigations in various solid tumors in human patients treated with anti-PD1 immunotherapy, we identified and validated circulating CD137 on CD8+ T cells as a predictive biomarker of response to treatment. Subsequently, the study focused on GBM, delving into CD137’s role in the anti-tumor immune response in human patients and murine models. In GBM patients, higher levels of infiltrated CD137+CD8+PD1+ T cells were negatively correlated with survival after surgery. Particularly, CD137 is more expressed in terminally exhausted T cells compared with progenitor ones, both in humans and mice. Hence, mice models treated with anti-CD137 showed an increase in T-cell activation and exhaustion inside the tumor and in the spleen, accompanied by augmented cytokine secretion within the tumor microenvironment. The study also explored the impact of hypoxia, a key factor in GBM immunosuppression, on T-cell exhaustion and tumor associated macrophages (TAM). Axitinib, a VEGFR-targeting TKI, was utilized to reduce the hypoxia-induced immunosuppression, and the targeting CD137 combination with axitinib resulted in increased overall survival and activation of lasting immunological memory as tested in brain tumor mouse model.
Conclusion: CD137 could represent a promising biomarker for immunotherapy response in solid tumors, including glioblastoma where immunotherapy fails.
CD137 appears to play an important role in the biological process of exhaustion of T cells in GBM. CD137 targeting combined with modulation of the tumor microenvironment represents a promising strategy to overcome the challenges associated with GBM immune unresponsiveness, providing new prospective for more effective and personalized immunotherapeutic treatments in GBM
Chicken-or-egg question: Which came first, extracellular vesicles or autoimmune diseases?
No full textExtracellular vesicles (EVs) have attracted great interest as contributors to autoimmune disease (AD) pathogenesis, owing to their immunomodulatory potential; they may also play a role in triggering tolerance disruption, by delivering auto-antigens. EVs are released by almost all cell types, and afford paracrine or distal cell communication, functioning as biological carriers of active molecules including lipids, proteins, and nucleic acids. Depending on stimuli from the external microenvironment or on their cargo, EVs can promote or suppress immune responses. ADs are triggered by inappropriate immune-system activation against the self, but their precise etiology is still poorly understood. Accumulating evidence indicates that lifestyle and diet have a strong impact on their clinical onset and development. However, to date the mechanisms underlying AD pathogenesis are not fully clarified, and reliable markers, which would provide early prediction and disease progression monitoring, are lacking. In this connection, EVs have recently been indicated as a promising source of AD biomarkers. Although EV isolation is currently based on differential centrifugation or density-gradient ultracentrifugation, the resulting co-isolation of contaminants (i.e., protein aggregates), and the pooling of all EVs in one sample, limit this approach to abundantly-expressed EVs. Flow cytometry is one of the most promising methods for detecting EVs as biomarkers, and may have diagnostic applications. Furthermore, very recent findings describe a new method for identifying and sorting EVs by flow cytometry from freshly collected body fluids, based on specific EV surface markers
Determination of theobromine, theophylline and caffeine in by-products of cupuacu and cacao seeds by high performance liquid chromatography
No full textHow to tackle the relationship between autoimmune diseases and diet: Well begun is half-done
No full textNutrition and immunity are closely related, and the immune system is composed of the most highly energy-consuming cells in the body. Much of the immune system is located within the GI tract, since it must deal with the huge antigenic load introduced with food. Moreover, the incidence of immune-mediated diseases is elevated in Westernized countries, where “transition nutrition” prevails, owing to the shift from traditional dietary patterns towards Westernized patterns. This ecological correlation has fostered increasing attempts to find evidence to support nutritional interventions aimed at managing and reducing the risk of immune-mediated diseases. Recent studies have described the impacts of single nutrients on markers of immune function, but the knowledge currently available is not sufficient to demonstrate the impact of specific dietary patterns on immune-mediated clinical disease endpoints. If nutritional scientists are to conduct quality research, one of many challenges facing them, in studying the complex interactions between the immune system and diet, is to develop improved tools for investigating eating habits in the context of immunomediated diseases
Individuazione degli aspetti ambientali significativi nella gestione di un impianto di termovalorizzazione di rifiuti urbani
No full text
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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