Author
Marie Vétizou
Other affiliations: French Institute of Health and Medical Research, Université Paris-Saclay, University of Paris-Sud ...read more
Bio: Marie Vétizou is an academic researcher from Institut Gustave Roussy. The author has contributed to research in topics: Immunotherapy & Gut flora. The author has an hindex of 16, co-authored 25 publications receiving 3291 citations. Previous affiliations of Marie Vétizou include French Institute of Health and Medical Research & Université Paris-Saclay.
Topics: Immunotherapy, Gut flora, Immune system, Blockade, Cytotoxic T cell
Papers
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University of Paris-Sud1, French Institute of Health and Medical Research2, Institut Gustave Roussy3, 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
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TL;DR: How a range of cancer-cell-autonomous cues, tumor-microenvironmental factors, and host-related influences might account for the heterogeneous responses and failures often encountered during therapies using immune-checkpoint blockade is reviewed.
747 citations
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TL;DR: In this article, a clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-programmed cell death protein 1 (PD-1) therapy for patients with advanced melanoma.
Abstract: Anti-programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma The composition of the gut microbiota correlates with anti-PD-1 efficacy in preclinical models and cancer patients To investigate whether resistance to anti-PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-PD-1 in patients with PD-1-refractory melanoma This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti-PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8-expressing myeloid cells Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes Collectively, our findings show that FMT and anti-PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of PD-1 advanced melanoma
540 citations
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TL;DR: The gut microbiota and its interactions with the host immune system play a role in oncogenesis and can alter the effectiveness of anticancer agents.
Abstract: Changes in the interactions among the gut microbiota, intestinal epithelium, and host immune system are associated with many diseases, including cancer. We discuss how environmental factors infuence this cross-talk during oncogenesis and tumor progression and how manipulations of the gut microbiota might improve the clinical activity of anticancer agents.
357 citations
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QIMR Berghofer Medical Research Institute1, Fred Hutchinson Cancer Research Center2, University of Western Australia3, Royal Brisbane and Women's Hospital4, University of Freiburg5, University of Minnesota6, Princess Alexandra Hospital7, University of Queensland8, Monash University, Clayton campus9, Lions Eye Institute10
TL;DR: Intervention of MHC class II expression by IECs in the ileum initiates lethal GVHD, and blockade of IL-12/23p40 may represent a readily translatable therapeutic strategy.
143 citations
Cited by
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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
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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
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TL;DR: As the molecular mechanisms of resistance to immunotherapy are elucidated, actionable strategies to prevent or treat them may be derived to improve clinical outcomes for patients.
3,131 citations
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University of California, San Francisco1, Cold Spring Harbor Laboratory2, Icahn School of Medicine at Mount Sinai3, Oregon Health & Science University4, Wistar Institute5, Huntsman Cancer Institute6, University of Maryland, Baltimore County7, La Jolla Institute for Allergy and Immunology8, University of Pennsylvania9, Harvard University10, University of Michigan11, Massachusetts Institute of Technology12
TL;DR: By parsing the unique classes and subclasses of tumor immune microenvironment (TIME) that exist within a patient’s tumor, the ability to predict and guide immunotherapeutic responsiveness will improve, and new therapeutic targets will be revealed.
Abstract: The clinical successes in immunotherapy have been both astounding and at the same time unsatisfactory. Countless patients with varied tumor types have seen pronounced clinical response with immunotherapeutic intervention; however, many more patients have experienced minimal or no clinical benefit when provided the same treatment. As technology has advanced, so has the understanding of the complexity and diversity of the immune context of the tumor microenvironment and its influence on response to therapy. It has been possible to identify different subclasses of immune environment that have an influence on tumor initiation and response and therapy; by parsing the unique classes and subclasses of tumor immune microenvironment (TIME) that exist within a patient's tumor, the ability to predict and guide immunotherapeutic responsiveness will improve, and new therapeutic targets will be revealed.
2,920 citations
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TL;DR: The wide range of immune-related adverse effects associated with immune checkpoint blockade can complicate this effective therapy and limit its use in patients with cancer.
Abstract: Side Effects of Immune Checkpoint Blockade The wide range of immune-related adverse effects associated with immune checkpoint blockade can complicate this effective therapy and limit its use in patients with cancer. This review surveys the adverse effects and their management.
2,658 citations