Commensal microbiota contributes to predicting the response to immune checkpoint inhibitors in non-small-cell lung cancer patients

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.

Automated summary

The study examined the microbiota in stool and sputum samples of metastatic NSCLC patients receiving immunotherapy, finding distinct signatures between gut and respiratory microbiota, with gut microbiota diversity associated with the response to anti-PD-1 treatment. Higher gut microbiota diversity indicated better response and longer progression-free survival, suggesting a potential predictive value. Analysis of responders and nonresponders showed differences in microbial composition, with Streptococcus abundance positively correlated with CD8(+) T cells, highlighting a relationship between microbiota and immunotherapy response in NSCLC patients. Gut and respiratory microbiota are promising biomarkers for screening suitable candidates for immune checkpoint inhibitor-based immunotherapy.