Author
Andreas Schlitzer
Other affiliations: Agency for Science, Technology and Research, Technische Universität München, Singapore Immunology Network ...read more
Bio: Andreas Schlitzer is an academic researcher from University of Bonn. The author has contributed to research in topics: Biology & Population. The author has an hindex of 36, co-authored 62 publications receiving 10544 citations. Previous affiliations of Andreas Schlitzer include Agency for Science, Technology and Research & Technische Universität München.
Topics: Biology, Population, Immunity, Medicine, Myeloid
Papers
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Institut Gustave Roussy1, French Institute of Health and Medical Research2, University of Paris-Sud3, Institut national de la recherche agronomique4, university of lille5, Paris Descartes University6, New York University7, Pasteur Institute8, Agency for Science, Technology and Research9, Albert Einstein College of Medicine10, Centre national de la recherche scientifique11, Paul Sabatier University12
TL;DR: A key role is revealed for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade, which is found to depend on distinct Bacteroides species in mice and patients.
Abstract: Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis–specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.
2,360 citations
French Institute of Health and Medical Research1, University of Paris-Sud2, Institut Gustave Roussy3, Harvard University4, Agency for Science, Technology and Research5, Pasteur Institute6, Institut national de la recherche agronomique7, University of Orléans8, University of Alabama at Birmingham9, Agro ParisTech10, University of Burgundy11
TL;DR: It is demonstrated that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram-positive bacteria into secondary lymphoid organs, which suggests that the gut microbiota help shape the anticancer immune response.
Abstract: Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate antitumor immune responses. Studying mouse models, we demonstrate that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram-positive bacteria into secondary lymphoid organs. There, these bacteria stimulate the generation of a specific subset of "pathogenic" T helper 17 (pT(H)17) cells and memory T(H)1 immune responses. Tumor-bearing mice that were germ-free or that had been treated with antibiotics to kill Gram-positive bacteria showed a reduction in pT(H)17 responses, and their tumors were resistant to cyclophosphamide. Adoptive transfer of pT(H)17 cells partially restored the antitumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response.
1,487 citations
Radboud University Nijmegen1, University of Bonn2, Université de Montréal3, University of Chicago4, University of Edinburgh5, Dresden University of Technology6, McGill University Health Centre7, McGill University8, Rockefeller University9, University of Cape Town10, Instituto de Medicina Molecular11, Icahn School of Medicine at Mount Sinai12, Eindhoven University of Technology13, University of Southern Denmark14, Memorial Sloan Kettering Cancer Center15, Cornell University16, Harvard University17, Broad Institute18, German Center for Neurodegenerative Diseases19, University of Massachusetts Medical School20
TL;DR: A group of leaders in the field define ‘trained immunity’ as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.
Abstract: Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been termed 'trained immunity', a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define 'trained immunity' as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.
1,116 citations
TL;DR: This work comprehensively map myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow, showing unexpected transcriptional priming toward seven differentiation fates but no progenitors with a mixed state.
905 citations
TL;DR: The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in vivo findings to advance DC-based clinical therapies.
718 citations
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TL;DR: An analytical strategy for integrating scRNA-seq data sets based on common sources of variation is introduced, enabling the identification of shared populations across data sets and downstream comparative analysis.
Abstract: Computational single-cell RNA-seq (scRNA-seq) methods have been successfully applied to experiments representing a single condition, technology, or species to discover and define cellular phenotypes. However, identifying subpopulations of cells that are present across multiple data sets remains challenging. Here, we introduce an analytical strategy for integrating scRNA-seq data sets based on common sources of variation, enabling the identification of shared populations across data sets and downstream comparative analysis. We apply this approach, implemented in our R toolkit Seurat (http://satijalab.org/seurat/), to align scRNA-seq data sets of peripheral blood mononuclear cells under resting and stimulated conditions, hematopoietic progenitors sequenced using two profiling technologies, and pancreatic cell 'atlases' generated from human and mouse islets. In each case, we learn distinct or transitional cell states jointly across data sets, while boosting statistical power through integrated analysis. Our approach facilitates general comparisons of scRNA-seq data sets, potentially deepening our understanding of how distinct cell states respond to perturbation, disease, and evolution.
7,741 citations
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
French Institute of Health and Medical Research1, Université Paris-Saclay2, Institut Gustave Roussy3, Pierre-and-Marie-Curie University4, Paris Diderot University5, Memorial Sloan Kettering Cancer Center6, University of Orléans7, Paris Descartes University8, Cornell University9, Aix-Marseille University10
TL;DR: It is found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition, and Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer.
Abstract: Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so. Metagenomics of patient stool samples at diagnosis revealed correlations between clinical responses to ICIs and the relative abundance of Akkermansia muciniphila Oral supplementation with A. muciniphila after FMT with nonresponder feces restored the efficacy of PD-1 blockade in an interleukin-12-dependent manner by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into mouse tumor beds.
3,258 citations
TL;DR: In high-income countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses.
3,257 citations
TL;DR: Clinical studies are beginning to define these factors as immune profiles that can predict responses to immunotherapy, suggesting that a broader view of cancer immunity is required.
Abstract: Immunotherapy is proving to be an effective therapeutic approach in a variety of cancers. But despite the clinical success of antibodies against the immune regulators CTLA4 and PD-L1/PD-1, only a subset of people exhibit durable responses, suggesting that a broader view of cancer immunity is required. Immunity is influenced by a complex set of tumour, host and environmental factors that govern the strength and timing of the anticancer response. Clinical studies are beginning to define these factors as immune profiles that can predict responses to immunotherapy. In the context of the cancer-immunity cycle, such factors combine to represent the inherent immunological status - or 'cancer-immune set point' - of an individual.
3,145 citations