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Milliat, F.

Publications and source records attributed to Milliat, F..

2 recordsLinked to original sources

Comparing cellular response to two radiation treatments based on key features visualization

MotivationIn modern treatment by radiotherapy, different irradiation modalities can be used, potentially producing different amounts of adverse effects. The differences between these modalities are often studied via two-sample time course in vitro experiments. The resulting data may be of high complexity, in which case simple methods are unadapted for extracting all the relevant information. MethodsIn this article we introduce network-based tools for the visualization of the key statistical features, extracted from the data. For the key features extraction we utilize a statistical framework performing estimation, clustering with alignment of temporal omic fold changes originating from two-sample time course data. ResultsThe approach was applied to real transcriptomic data obtained with two different types of irradiation. The results were analyzed using biological literature and enrichment analysis, thus validating the robustness of the proposed tools as well as achieving better understanding of the differences in the impact of the treatments in question. Availability and implementationPython package freely available here: https://github.com/parsenteva/scanofc. Contactpolina.arsenteva@u-bourgogne.fr

bioinformatics↗

TGFβ receptor inhibition unleashes interferon-β production by tumor-associated macrophages and enhances radiotherapy efficacy

BackgroundTransforming growth factor-beta (TGF{beta}) can limit the efficacy of cancer treatments, including radiotherapy (RT), by inducing an immunosuppressive tumor environment. The association of TGF{beta} with impaired T cell infiltration and antitumor immunity is known, but the mechanisms by which TGF{beta} participates in immune cell exclusion and limits the efficacy of antitumor therapies warrant further investigations. MethodsWe used the clinically relevant TGF{beta} receptor 2 (TGF{beta}R2)-neutralizing antibody MT1 and the small molecule TGF{beta}R1 inhibitor LY3200882 and evaluated their efficacy in combination with RT against murine orthotopic models of head and neck and lung cancer. ResultsWe demonstrated that TGF{beta} pathway inhibition strongly increased the efficacy of RT. TGF{beta}R2 antibody upregulated interferon beta (IFN{beta}) expression in tumor-associated macrophages (TAMs) within the irradiated tumors and favored T cell infiltration at the periphery and within the core of the tumor lesions. We highlighted that both the antitumor efficacy and inhibition of immune exclusion observed with the combination of MT1 and RT were dependent on type I interferon signaling. ConclusionsThese data shed new light on the role of TGF{beta} in limiting the efficacy of RT, identifying a novel mechanism involving the inhibition of macrophage-derived type I interferon production, and fostering the use of TGF{beta}R inhibition in combination with RT in therapeutic strategies for the management of head and neck and lung cancer.

cancer biology↗