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

Abstract

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.

Checkpoint Inhibitor Pneumonitis Induced by Anti-PD-1/PD-L1 Therapy in Non-Small-Cell Lung Cancer: Occurrence and Mechanism

“…Zhang et al. ( 134 ) found that featured respiratory microbes such as enriched Streptococcus may enhance antitumor immune responses by increasing antigen presentation and effector T cell function, which may increase the incidence of irAEs, including CIP.…”

Analysis of Gut Microbiota Signature and Microbe-Disease Progression Associations in Locally Advanced Non-Small Cell Lung Cancer Patients Treated With Concurrent Chemoradiotherapy

“…Recent studies have demonstrated that gut microbiome is associated with NSCLC progression. Patients with higher gut microbiota alpha diversity ( Zhang C. et al., 2021 ), and those enriched in some microbes, such as Phascolarctobacterium ( Zhang F. et al., 2021 ), Ruminococcaceae UCG 13 , and Agathobacter ( Hakozaki et al., 2020 ), were found to have better PFS. In the current study, we found that the long-PFS group had the highest F/B value and significantly higher diversity in Fungi, Archaea, and Viruses among three groups.…”

The Lung Microbiome during Health and Disease

“…Of note, recent evidence has demonstrates that gut dysbiosis might impair the systemic response to efficacy in advanced cancer patients. Studies have documented that it is possible to predict based upon their gut microbiome whether the cancer patients are hyper-responder or non-responder to immune checkpoint inhibitor-based immunotherapy [ 86 ]. The alpha diversity between the gut and respiratory microbiota was not linked, and only the gut microbiota alpha diversity was associated with anti-programmed cell death-1 response.…”

“…The alpha diversity between the gut and respiratory microbiota was not linked, 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 [ 86 ]. Antitumor immunotherapy is promising, however, very costly, leading to an increase in the social-economic burden.…”