Increased Th17 activation and gut microbiota diversity are associated with pembrolizumab-triggered tuberculosis.
INTRODUCTION
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.


MATERIALS AND METHODS
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.


RESULTS
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.


DISCUSSION
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.
['Zhang|Yun-Bin|YB|', 'Liu|Shi-Jia|SJ|', 'Hu|Zhi-Dong|ZD|', 'Zhou|Ji-Xue|JX|', 'Wang|Yin-Zhen|YZ|', 'Fang|Bing|B|', 'Wong|Ka-Wing|KW|', 'Xia|Fan|F|http://orcid.org/0000-0003-3932-6465']
D061067:Antibodies, Monoclonal, Humanized D000995:Antitubercular Agents D004269:DNA, Bacterial D066264:Datasets as Topic D000069196:Gastrointestinal Microbiome D006801:Humans D054019:Immune Reconstitution Inflammatory Syndrome D008168:Lung D008175:Lung Neoplasms D008297:Male D008875:Middle Aged D009169:Mycobacterium tuberculosis D018720:Prevotella D061026:Programmed Cell Death 1 Receptor D012336:RNA, Ribosomal, 16S D058504:Th17 Cells D014057:Tomography, X-Ray Computed D014376:Tuberculosis
Th17 activation Gut microbiota diversity Tuberculosis Immune reconstitution inflammatory syndrome (IRIS) Pembrolizumab