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Author

Romain Banchereau

Bio: Romain Banchereau is an academic researcher from Genentech. The author has contributed to research in topics: Atezolizumab & Immune system. The author has an hindex of 27, co-authored 41 publications receiving 5910 citations. Previous affiliations of Romain Banchereau include University of Texas Southwestern Medical Center & Baylor University Medical Center.
Topics: Atezolizumab, Immune system, CD8, T cell, Medicine

Papers
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Journal ArticleDOI
22 Feb 2018-Nature
TL;DR: Tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent were examined and major determinants of clinical outcome were identified and suggested that TGFβ shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T-cell infiltration.
Abstract: Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here we examined tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response to treatment was associated with CD8+ T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden. Lack of response was associated with a signature of transforming growth factor β (TGFβ) signalling in fibroblasts. This occurred particularly in patients with tumours, which showed exclusion of CD8+ T cells from the tumour parenchyma that were instead found in the fibroblast- and collagen-rich peritumoural stroma; a common phenotype among patients with metastatic urothelial cancer. Using a mouse model that recapitulates this immune-excluded phenotype, we found that therapeutic co-administration of TGFβ-blocking and anti-PD-L1 antibodies reduced TGFβ signalling in stromal cells, facilitated T-cell penetration into the centre of tumours, and provoked vigorous anti-tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding patient outcome in this setting and suggests that TGFβ shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T-cell infiltration.

2,808 citations

Journal ArticleDOI
19 Aug 2010-Nature
TL;DR: A hitherto underappreciated role of type I IFN-αβ signalling in the pathogenesis of TB is demonstrated, which has implications for vaccine and therapeutic development and a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic are provided.
Abstract: Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis, is a major cause of morbidity and mortality worldwide. Efforts to control it are hampered by difficulties with diagnosis, prevention and treatment. Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease. Current tests, however, cannot identify which individuals will develop disease. The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines. Here we identify a whole-blood 393 transcript signature for active TB in intermediate and high-burden settings, correlating with radiological extent of disease and reverting to that of healthy controls after treatment. A subset of patients with latent TB had signatures similar to those in patients with active TB. We also identify a specific 86-transcript signature that discriminates active TB from other inflammatory and infectious diseases. Modular and pathway analysis revealed that the TB signature was dominated by a neutrophil-driven interferon (IFN)-inducible gene profile, consisting of both IFN-gamma and type I IFN-alphabeta signalling. Comparison with transcriptional signatures in purified cells and flow cytometric analysis suggest that this TB signature reflects changes in cellular composition and altered gene expression. Although an IFN-inducible signature was also observed in whole blood of patients with systemic lupus erythematosus (SLE), their complete modular signature differed from TB, with increased abundance of plasma cell transcripts. Our studies demonstrate a hitherto underappreciated role of type I IFN-alphabeta signalling in the pathogenesis of TB, which has implications for vaccine and therapeutic development. Our study also provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic.

1,588 citations

Journal ArticleDOI
21 Apr 2016-Cell
TL;DR: This study uncovers the molecular heterogeneity of SLE and provides an explanation for the failure of clinical trials, and personalized immunomonitoring uncovered individual correlates of disease activity that enabled patient stratification into seven groups, supported by patient genotypes.

523 citations

Journal ArticleDOI
TL;DR: A single-arm multicenter phase 2 trial demonstrates clinical efficacy of neoadjuvant PD-L1 blockade in patients with resectable muscle-invasive bladder cancer ineligible for cisplatin and examines biomarkers associated with patient outcome.
Abstract: Antibodies targeting PD-1 or its ligand 1 PD-L1 such as atezolizumab, have great efficacy in a proportion of metastatic urothelial cancers1,2. Biomarkers may facilitate identification of these responding tumors3. Neoadjuvant use of these agents is associated with pathological complete response in a spectrum of tumors, including urothelial cancer4-7. Sequential tissue sampling from these studies allowed for detailed on-treatment biomarker analysis. Here, we present a single-arm phase 2 study, investigating two cycles of atezolizumab before cystectomy in 95 patients with muscle-invasive urothelial cancer (ClinicalTrials.gov identifier: NCT02662309). Pathological complete response was the primary endpoint. Secondary endpoints focused on safety, relapse-free survival and biomarker analysis. The pathological complete response rate was 31% (95% confidence interval: 21-41%), achieving the primary efficacy endpoint. Baseline biomarkers showed that the presence of preexisting activated T cells was more prominent than expected and correlated with outcome. Other established biomarkers, such as tumor mutational burden, did not predict outcome, differentiating this from the metastatic setting. Dynamic changes to gene expression signatures and protein biomarkers occurred with therapy, whereas changes in DNA alterations with treatment were uncommon. Responding tumors showed predominant expression of genes related to tissue repair after treatment, making tumor biomarker interpretation challenging in this group. Stromal factors such as transforming growth factor-β and fibroblast activation protein were linked to resistance, as was high expression of cell cycle gene signatures after treatment.

362 citations


Cited by
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Journal ArticleDOI
24 Jun 2021-Cell
TL;DR: Weighted-nearest neighbor analysis as mentioned in this paper is an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities.

3,369 citations

Journal ArticleDOI
Lorenzo Galluzzi1, Lorenzo Galluzzi2, Ilio Vitale3, Stuart A. Aaronson4  +183 moreInstitutions (111)
TL;DR: The Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives.
Abstract: Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

3,301 citations

Posted ContentDOI
12 Oct 2020-bioRxiv
TL;DR: ‘weighted-nearest neighbor’ analysis is introduced, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities.
Abstract: The simultaneous measurement of multiple modalities, known as multimodal analysis, represents an exciting frontier for single-cell genomics and necessitates new computational methods that can define cellular states based on multiple data types. Here, we introduce ‘weighted-nearest neighbor’ analysis, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of hundreds of thousands of human white blood cells alongside a panel of 228 antibodies to construct a multimodal reference atlas of the circulating immune system. We demonstrate that integrative analysis substantially improves our ability to resolve cell states and validate the presence of previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets, and to interpret immune responses to vaccination and COVID-19. Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets, including paired measurements of RNA and chromatin state, and to look beyond the transcriptome towards a unified and multimodal definition of cellular identity. Availability Installation instructions, documentation, tutorials, and CITE-seq datasets are available at http://www.satijalab.org/seurat

2,924 citations

Journal ArticleDOI
Robert M. Samstein1, Chung-Han Lee1, Chung-Han Lee2, Alexander N. Shoushtari1, Alexander N. Shoushtari2, Matthew D. Hellmann2, Matthew D. Hellmann1, Ronglai Shen1, Yelena Y. Janjigian2, Yelena Y. Janjigian1, David Barron1, Ahmet Zehir1, Emmet Jordan1, Antonio Omuro1, Thomas Kaley1, Sviatoslav M. Kendall1, Robert J. Motzer2, Robert J. Motzer1, A. Ari Hakimi1, Martin H. Voss1, Martin H. Voss2, Paul Russo1, Jonathan E. Rosenberg1, Jonathan E. Rosenberg2, Gopa Iyer1, Gopa Iyer2, Bernard H. Bochner1, Dean F. Bajorin1, Dean F. Bajorin2, Hikmat Al-Ahmadie1, Jamie E. Chaft1, Jamie E. Chaft2, Charles M. Rudin2, Charles M. Rudin1, Gregory J. Riely2, Gregory J. Riely1, Shrujal S. Baxi1, Shrujal S. Baxi2, Alan L. Ho1, Alan L. Ho2, Richard J. Wong1, David G. Pfister1, David G. Pfister2, Jedd D. Wolchok1, Jedd D. Wolchok2, Christopher A. Barker1, Philip H. Gutin1, Cameron Brennan1, Viviane Tabar1, Ingo K. Mellinghoff1, Lisa M. DeAngelis1, Charlotte E. Ariyan1, Nancy Y. Lee1, William D. Tap2, William D. Tap1, Mrinal M. Gounder1, Mrinal M. Gounder2, Sandra P. D'Angelo1, Sandra P. D'Angelo2, Leonard B. Saltz1, Leonard B. Saltz2, Zsofia K. Stadler2, Zsofia K. Stadler1, Howard I. Scher2, Howard I. Scher1, José Baselga1, José Baselga2, Pedram Razavi1, Pedram Razavi2, Christopher A. Klebanoff1, Christopher A. Klebanoff2, Rona Yaeger1, Rona Yaeger2, Neil H. Segal2, Neil H. Segal1, Geoffrey Y. Ku1, Geoffrey Y. Ku2, Ronald P. DeMatteo1, Marc Ladanyi1, Naiyer A. Rizvi3, Michael F. Berger1, Nadeem Riaz1, David B. Solit1, Timothy A. Chan1, Luc G. T. Morris1 
TL;DR: Analysis of advanced cancer patients treated with immune-checkpoint inhibitors shows that tumor mutational burden, as assessed by targeted next-generation sequencing, predicts survival after immunotherapy across multiple cancer types.
Abstract: Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in selected cancer types suggest that tumor mutational burden (TMB) may predict clinical response to ICI. To examine this association more broadly, we analyzed the clinical and genomic data of 1,662 advanced cancer patients treated with ICI, and 5,371 non-ICI-treated patients, whose tumors underwent targeted next-generation sequencing (MSK-IMPACT). Among all patients, higher somatic TMB (highest 20% in each histology) was associated with better overall survival. For most cancer histologies, an association between higher TMB and improved survival was observed. The TMB cutpoints associated with improved survival varied markedly between cancer types. These data indicate that TMB is associated with improved survival in patients receiving ICI across a wide variety of cancer types, but that there may not be one universal definition of high TMB.

2,343 citations

Journal ArticleDOI
TL;DR: Neutrophils have long been viewed as the final effector cells of an acute inflammatory response, with a primary role in the clearance of extracellular pathogens, but more recent evidence has extended the functions of these cells.
Abstract: Neutrophils have long been viewed as the final effector cells of an acute inflammatory response, with a primary role in the clearance of extracellular pathogens. However, more recent evidence has extended the functions of these cells. The newly discovered repertoire of effector molecules in the neutrophil armamentarium includes a broad array of cytokines, extracellular traps and effector molecules of the humoral arm of the innate immune system. In addition, neutrophils are involved in the activation, regulation and effector functions of innate and adaptive immune cells. Accordingly, neutrophils have a crucial role in the pathogenesis of a broad range of diseases, including infections caused by intracellular pathogens, autoimmunity, chronic inflammation and cancer.

2,318 citations