📇 Rhumatologue ·

MME ELIANE CENDRIER-SCHAEFFERT

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Auteur de référence en rhumatologie
45 articles scientifiques publiés — un praticien à la pointe de la recherche

Rhumatologue

RPPS 10002111820

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Top publications · les plus citées

Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma

Cell · 2018

📚 1488 citations🎯 RCR 43.41Top 0% NIH🔓 Open Access📄 PDF gratuit ↗

Resistance to checkpoint blockade therapy through inactivation of antigen presentation

Nature communications · 2017

📚 792 citations🎯 RCR 22.30Top 1% NIH🔓 Open Access📄 PDF gratuit ↗

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AbstractTreatment with immune checkpoint blockade (CPB) therapies often leads to prolonged responses in patients with metastatic melanoma, but the common mechanisms of primary and acquired resistance to these agents remain incompletely characterized and have yet to be validated in large cohorts. By analyzing longitudinal tumor biopsies from 17 metastatic melanoma patients treated with CPB therapies, we observed point mutations, deletions or loss of heterozygosity (LOH) in beta-2-microglobulin (B2M), an essential component of MHC class I antigen presentation, in 29.4% of patients with progressing disease. In two independent cohorts of melanoma patients treated with anti-CTLA4 and anti-PD1, respectively, we find that B2M LOH is enriched threefold in non-responders (~30%) compared to responders (~10%) and associated with poorer overall survival. Loss of both copies of B2M is found only in non-responders. B2M loss is likely a common mechanism of resistance to therapies targeting CTLA4 or PD1.

Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids

Cancer discovery · 2018

📚 470 citations🎯 RCR 14.70Top 1% NIH

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Abstract Ex vivo systems that incorporate features of the tumor microenvironment and model the dynamic response to immune checkpoint blockade (ICB) may facilitate efforts in precision immuno-oncology and the development of effective combination therapies. Here, we demonstrate the ability to interrogate ex vivo response to ICB using murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS). MDOTS/PDOTS isolated from mouse and human tumors retain autologous lymphoid and myeloid cell populations and respond to ICB in short-term three-dimensional microfluidic culture. Response and resistance to ICB was recapitulated using MDOTS derived from established immunocompetent mouse tumor models. MDOTS profiling demonstrated that TBK1/IKKϵ inhibition enhanced response to PD-1 blockade, which effectively predicted tumor response in vivo. Systematic profiling of secreted cytokines in PDOTS captured key features associated with response and resistance to PD-1 blockade. Thus, MDOTS/PDOTS profiling represents a novel platform to evaluate ICB using established murine models as well as clinically relevant patient specimens. Significance: Resistance to PD-1 blockade remains a challenge for many patients, and biomarkers to guide treatment are lacking. Here, we demonstrate feasibility of ex vivo profiling of PD-1 blockade to interrogate the tumor immune microenvironment, develop therapeutic combinations, and facilitate precision immuno-oncology efforts. Cancer Discov; 8(2); 196–215. ©2017 AACR. See related commentary by Balko and Sosman, p. 143. See related article by Deng et al., p. 216. This article is highlighted in the In This Issue feature, p. 127

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MME ELIANE CENDRIER-SCHAEFFERT

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Top publications · les plus citées

Publications scientifiques (45) — classées par pathologie

Transversal36

IA en rhumatologie2

Lupus2

Case report / série1

Épidémiologie & registres1

Essai clinique1

Recommandations1

Risque cardio-vasculaire1

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