Immunosenescence (iSenescence) correlates with progression (PD) to PD-(L)1 inhibitors (IO) and not to platinum-chemotherapy (PCT) in advanced non-small cell lung cancer (aNSCLC) patients (pts)

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Enabling reactive cities with the iFLUX middleware

This paper presents the iFLUX middleware, designed to provide a lightweight integration solution for Smart City applications. Based on three core abstractions, namely event sources, action targets and rules, iFLUX makes it very easy to expose sensors and actuators through REST APIs so that they can be integrated in application-level workflows. Sensors and actuators can be smart objects integrating hardware and software, but can also be pure software services. In the paper, we introduce the iFLUX programming model and describe how it has been implemented in a middleware platform. We also report on how the platform has been used and evaluated in various contexts. While iFLUX has been initially designed in the context of Smart City applications, it is generic and applicable to other domains where hardware and software components are connected through the Web

Deep phenotyping of immune cell populations by optimized and standardized flow cytometry analyses

International audienceMulticolor flow cytometry is a technology of choice for phenotyping of immune cells, and it can be used routinely for the follow up of patients in clinical trials. But it is challenging to define combinations of conjugated antibodies that efficiently allow the detailed analysis of major immune cell subsets and the identification of rare cell populations. In a collaborative work among the Immunology, Immunopathology, Immunotherapy (I3) laboratory, and the laboratory of immunomonitoring in oncology (L.I.O), we developed and validated 12 different 10‐color flow cytometry panels that allow the deep immunophenotyping of cells from whole blood for the follow up of autoimmune and cancer patients. Here, we describe these optimized flow cytometry panels, showing that they provide the advanced analysis of T cells (including regulatory T cells), B cells, NK cells, MAIT cells, myeloid cells, monocytes, and dendritic cells. Most of the panels have been dried to improve standardization of the labeling and the entire procedure can be performed on less than 2 ml of whole blood. These deep immunophenotyping flow cytometry panels constitute a powerful tool for the monitoring of immune blood cells and will hopefully lead to the discovery of new biomarkers and potential therapeutic targets in autoimmune and cancer clinical trials

Deep phenotyping of immune cell populations by optimized and standardized flow cytometry analyses

International audienceMulticolor flow cytometry is a technology of choice for phenotyping of immune cells, and it can be used routinely for the follow up of patients in clinical trials. But it is challenging to define combinations of conjugated antibodies that efficiently allow the detailed analysis of major immune cell subsets and the identification of rare cell populations. In a collaborative work among the Immunology, Immunopathology, Immunotherapy (I3) laboratory, and the laboratory of immunomonitoring in oncology (L.I.O), we developed and validated 12 different 10‐color flow cytometry panels that allow the deep immunophenotyping of cells from whole blood for the follow up of autoimmune and cancer patients. Here, we describe these optimized flow cytometry panels, showing that they provide the advanced analysis of T cells (including regulatory T cells), B cells, NK cells, MAIT cells, myeloid cells, monocytes, and dendritic cells. Most of the panels have been dried to improve standardization of the labeling and the entire procedure can be performed on less than 2 ml of whole blood. These deep immunophenotyping flow cytometry panels constitute a powerful tool for the monitoring of immune blood cells and will hopefully lead to the discovery of new biomarkers and potential therapeutic targets in autoimmune and cancer clinical trials

COVID-19 stigmatization after the development of effective vaccines: Vaccination behavior, attitudes, and news sources.

ObjectiveTo compare COVID-19 stigmatization at two pandemic time points (1) August 2020-during lockdowns and prior to vaccine rollout, and (2) May 2021-during vaccine rollout, when approximately half of U.S. adults were vaccinated.MethodsComparison of COVID19-related stigmatization and associated factors in two national internet surveys conducted in August 2020 (N = 517) and May 2021 (N = 812). Factors associated with endorsing stigmatization were identified using regression analysis. The main outcomes included endorsement of stigmatization and behavioral restrictions towards persons with COVID-19 and towards persons of Chinese descent. A previously developed "stigmatizing attitudes and behavioral restrictions" scale was adapted to measure the intersection of negative attitudes toward COVID-19 disease and negative attitudes toward persons of Chinese descent.ResultsCOVID-19 related stigmatization declined significantly from August 2020 to May 2021. Many factors were associated with stigmatizing in both surveys: full time employment, Black race, Hispanic ethnicity, worry about contracting COVID-19, probable depression, and Fox News and social media as sources of information (all positively associated), and self-assessed knowledge about COVID-19, contact with Chinese individuals, and publicly funded news as sources (all negatively associated). Positive attitudes toward vaccination were associated with stigmatization.ConclusionsCOVID-19 related stigmatization reduced substantially over these two points in the pandemic, with many continuities in the factors associated with stigmatizing. Despite the reduction in stigmatizing, however, some stigmatizing attitudes for both COVID-19 and Chinese individuals remained

Phase II and biomarker study of programmed cell death protein 1 inhibitor nivolumab and metronomic cyclophosphamide in paediatric relapsed/refractory solid tumours: Arm G of AcSé-ESMART, a trial of the European Innovative Therapies for Children With Cancer Consortium

International audienc

Integrating Circulating Biomarkers in the Immune Checkpoint Inhibitor Treatment in Lung Cancer

Immune checkpoint inhibitors are now a cornerstone of treatment for non-small cell lung cancer (NSCLC). Tissue-based assays, such as Programmed cell death protein 1 (PD-L1) expression or mismatch repair deficiency/microsatellite instability (MMRD/MSI) status, are approved as treatment drivers in various settings, and represent the main field of research in biomarkers for immunotherapy. Nonetheless, responses have been observed in patients with negative PD-L1 or low tumor mutational burden. Some aspects of biomarker use remain poorly understood and sub-optimal, in particular tumoral heterogeneity, time-evolving sampling, and the ability to detect patients who are unlikely to respond. Moreover, tumor biopsies offer little insight into the host’s immune status. Circulating biomarkers offer an alternative non-invasive solution to address these pitfalls. Here, we summarize current knowledge on circulating biomarkers while using liquid biopsies in patients with lung cancer who receive treatment with immune checkpoint inhibitors, in terms of their potential as being predictive of outcome as well as their role in monitoring ongoing treatment. We address host biomarkers, notably circulating immune cells and soluble systemic immune and inflammatory markers, and also review tumor markers, including blood-based tumor mutational burden, circulating tumor cells, and circulating tumor DNA. Technical requirements are discussed along with the current limitations that are associated with these promising biomarkers

Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer

International audienceGut microbiota composition influences the clinical benefit of immune checkpoints in patients with advanced cancer but mechanisms underlying this relationship remain unclear. Molecular mechanism whereby gut microbiota influences immune responses is mainly assigned to gut microbial metabolites. Short-chain fatty acids (SCFA) are produced in large amounts in the colon through bacterial fermentation of dietary fiber. We evaluate in mice and in patients treated with anti-CTLA-4 blocking mAbs whether SCFA levels is related to clinical outcome. High blood butyrate and propionate levels are associated with resistance to CTLA-4 blockade and higher proportion of Treg cells. In mice, butyrate restrains anti-CTLA-4-induced up-regulation of CD80/CD86 on dendritic cells and ICOS on T cells, accumulation of tumor-specific T cells and memory T cells. In patients, high blood butyrate levels moderate ipilimumab-induced accumulation of memory and ICOS + CD4 + T cells and IL-2 impregnation. Altogether, these results suggest that SCFA limits anti-CTLA-4 activity