3 results
Search Results
2. Immune checkpoint inhibitors unleash pathogenic immune responses against the microbiota.
- Author
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Zishuo Ian Hu, Link, Verena M., Lima-Junior, Djalma S., Delaleu, Jérémie, Bouladoux, Nicolas, Seong-Ji Han, Collins, Nicholas, and Belkaid, Yasmine
- Subjects
IMMUNE checkpoint inhibitors ,IMMUNE response ,DRUG side effects ,T cells ,LABORATORY mice - Abstract
Immune checkpoint inhibitors (ICIs) are essential components of the cancer therapeutic armamentarium. While ICIs have demonstrated remarkable clinical responses, they can be accompanied by immune-related adverse events (irAEs). These inflammatory side effects are of unclear etiology and impact virtually all organ systems, with the most common being sites colonized by the microbiota such as the skin and gastrointestinal tract. Here, we establish a mouse model of commensal bacteria-driven skin irAEs and demonstrate that immune checkpoint inhibition unleashes commensal-specific inflammatory T cell responses. These aberrant responses were dependent on production of IL-17 by commensal-specific T cells and induced pathology that recapitulated the cutaneous inflammation seen in patients treated with ICIs. Importantly, aberrant T cell responses unleashed by ICIs were sufficient to perpetuate inflammatory memory responses to the microbiota months following the cessation of treatment. Altogether, we have established a mouse model of skin irAEs and reveal that ICIs unleash aberrant immune responses against skin commensals, with long-lasting inflammatory consequences. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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3. Immunological exhaustion: How to make a disparate concept operational?
- Author
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Thomas Pradeu, Maël Lemoine, Hannah Kaminski, Immunology from Concept and Experiments to Translation (ImmunoConcept), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), European Project: 637647,H2020,ERC-2014-STG,IDEM(2015), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Viral Diseases ,T-Lymphocytes ,[SDV]Life Sciences [q-bio] ,Review ,medicine.disease_cause ,Lung and Intrathoracic Tumors ,[SHS.HISPHILSO]Humanities and Social Sciences/History, Philosophy and Sociology of Sciences ,White Blood Cells ,Medical Conditions ,0302 clinical medicine ,Animal Cells ,Immunopathology ,Cellular types ,Medicine and Health Sciences ,Cytotoxic T cell ,Biology (General) ,Immune Response ,0303 health sciences ,humanities ,Infectious Diseases ,Oncology ,Nephrology ,Renal Cancer ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Cell biology ,Blood cells ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,QH301-705.5 ,Immune Cells ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,education ,T cells ,Cytotoxic T cells ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Microbiology ,Immune System Phenomena ,03 medical and health sciences ,Immune system ,Virology ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,030304 developmental biology ,Colorectal Cancer ,Hepatitis B virus ,Biology and life sciences ,business.industry ,Cancers and Neoplasms ,Cancer ,Covid 19 ,RC581-607 ,medicine.disease ,Non-Small Cell Lung Cancer ,Parasitology ,Immunologic diseases. Allergy ,business ,030215 immunology - Abstract
In this essay, we show that 3 distinct approaches to immunological exhaustion coexist and that they only partially overlap, generating potential misunderstandings. Exploring cases ranging from viral infections to cancer, we propose that it is crucial, for experimental and therapeutic purposes, to clarify these approaches and their interconnections so as to make the concept of exhaustion genuinely operational., Author summary In this essay, we have written a critical review on immunological exhaustion. We believe that this widely used concept often remains in fact imprecise because there exist 3 different approaches to exhaustion, namely, in terms of dysfunction, cause, and marker, and those are not sufficiently well distinguished and articulated in most scientific papers. We also propose to talk about “exhaustion” for and only for the phenomena in which all 3 approaches are aligned. This can be called the “convergence strategy”: T cells would be described as “exhausted” if and only if they are simultaneously dysfunctional, express given markers such as programmed cell death protein 1 (PD-1), and induced by a specific cause such as chronicity. This strategy could be perfectly reasonable, and we see much value in adopting it, because it would force everyone to be more specific and rigorous when talking about exhaustion. Clarifying the characteristics of cells defined as “exhausted,” and using a convergent strategy to define T-cell exhaustion could have major experimental and clinical consequences, including for viral infections such as the Coronavirus Disease 2019 (COVID-19).
- Published
- 2021
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