Increased Th17 activation and gut microbiota diversity are associated with pembrolizumab-triggered tuberculosis
| Autor: | Yin-Zhen Wang, Ji-Xue Zhou, Bing Fang, Zhi-Dong Hu, Ka-Wing Wong, Fan Xia, Shi-Jia Liu, Yun-Bin Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
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Bacterial Male Cancer Research Lung Neoplasms T cell Immunology Population Programmed Cell Death 1 Receptor Antitubercular Agents Prevotella Datasets as Topic Inflammation Pembrolizumab Gut flora Antibodies Monoclonal Humanized 03 medical and health sciences 0302 clinical medicine Immune reconstitution inflammatory syndrome Immune Reconstitution Inflammatory Syndrome RNA Ribosomal 16S Immunology and Allergy Medicine Humans Tuberculosis Lung cancer education Lung education.field_of_study biology business.industry Mycobacterium tuberculosis Middle Aged medicine.disease biology.organism_classification Gastrointestinal Microbiome medicine.anatomical_structure Oncology Th17 Cells medicine.symptom business Cell activation Tomography X-Ray Computed 030215 immunology |
| Zdroj: | Cancer immunology, immunotherapy : CII. 69(12) |
| ISSN: | 1432-0851 |
| Popis: | A hypersensitivity response akin to immune reconstitution inflammatory syndrome (IRIS) has been proposed as a mechanism responsible for anti-PD-1 therapy-induced tuberculosis. IRIS is associated with enhanced activation of IL-17A-expressing CD4 + T cells (Th17). Gut microbiota is thought to be linked to pulmonary inflammation through the gut-lung axis. We used ImmuCellAI to investigate the T cell population in lung cancer and tuberculosis samples. Then, we applied flow cytometry to monitor the expression levels of the Th17 cell activation marker CD38 in the peripheral blood of a patient experiencing adverse events, including tuberculosis, in response to pembrolizumab. The gut microbiome was examined by 16S rRNA sequencing to examine the alterations caused by pembrolizumab. The percentage of Th17 cells was increased in both lung cancer and tuberculosis. FACS analysis showed that pembrolizumab induced substantial CD38 expression in Th17 cells. The patient’s fecal samples showed that the diversity of the gut microbiota was significantly increased in response to the pembrolizumab cycle. One enriched genus was Prevotella, which has previously been linked to lung inflammation and Th17 immune activation. The observed Th17 activation in our patient was consistent with a role of Th17-mediated IRIS in pembrolizumab-triggered tuberculosis. Pembrolizumab might trigger airway inflammation with a Th17 phenotype through microbiota interactions in the gut-lung axis. |
| Databáze: | OpenAIRE |
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