Immunotherapy against cancer, through immune checkpoint inhibitors targeting the programmed cell death‐1/programmed cell death‐ligand 1 axis, is particularly successful in tumors by relieving the immune escape. However, interindividual responses to immunotherapy are often heterogeneous. Therefore, it is essential to screen out predictive tumor biomarkers. In this study, we analyzed the commensal microbiota in stool samples and paired sputum samples from 75 metastatic non‐small‐cell lung cancer (NSCLC) patients at baseline and during treatment with immune checkpoint inhibitors. Results showed distinct microbes’ signatures between the gut microbiota and paired respiratory microbiota. The alpha diversity between the gut and respiratory microbiota was uncorrelated, and only the gut microbiota alpha diversity was associated with anti‐programmed cell death‐1 response. Higher gut microbiota alpha diversity indicated better response and more prolonged progression‐free survival. Comparison of bacterial communities between responders and nonresponders showed some favorable/unfavorable microbes enriched in responders/nonresponders, indicating that commensal microbiota had potential predictive value for the response to immune checkpoint inhibitors. Generally, some rare low abundance gut microbes and high abundance respiratory microbes lead to discrepancies in microbial composition between responders and nonresponders. A significant positive correlation was observed between the abundance of Streptococcus and CD8+ T cells. These results highlighted the intimate relationship between commensal microbiota and the response to immunotherapy in NSCLC patients. Gut microbiota and respiratory microbiota are promising biomarkers to screen suitable candidates who are likely to benefit from immune checkpoint inhibitor‐based immunotherapy.
The worldwide occurrence of cyanobacterial blooms makes it necessary to perform environmental risk assessment procedures to monitor the effects of microcytins on fish. Oxidative stress biomarkers are valuable tools in this regard. Considering that zebrafish (Danio rerio) is a common model species in fish toxicology and the zebrafish gill is potentially useful in screening waterborne pollutants, this study investigated the oxidative stress response in zebrafish gill exposed to subchronic microcystin-LR (MCLR) concentrations (2 or 20 μg/l) via measurement of toxin accumulation, protein phosphatase (PP) activity, and the antioxidant parameters (glutathione-S-transferase-GST; glutathione-GSH; superoxide dismutase-SOD; catalase-CAT; glutathione peroxide-GPx; glutathione reductase-GR), as well as levels of hydroxyl radical (OH) and lipid peroxidation (LPO). The results showed that after 30 days exposure, MCLR accumulated in zebrafish gill and MCLR exposure induced PP activity in gill. A linear inhibition of GST activity and GSH content was observed in the gills, revealing that they were involved in the first step of MCLR detoxification. The 2 μg/l MCLR treatment neglectably affected OH content and the antioxidant enzymes (SOD, CAT, GPx, and GR), however oxidative stress was induced under the 20 μg/l MCLR treatment in which an enhanced OH content and alterations of the antioxidant enzymes were observed in the treated gills, although both treatments exerted little effect on LPO level. The principal component analysis results indicated that the most sensitive biomarkers of MCLR exposure were GST and GSH in zebrafish gill. So, D. rerio could be regarded as a suitable bioindicator of MCLR exposure by measuring CAT, GR, GST, and GSH as biomarkers.
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