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作者

Chufeng Zhang, Jixin Wang, Zhongwen Sun, Yufeng Cao, Zhengshuai Mu, Xuming Ji

作者单位

College of Chinese Traditional Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250000, China. Zhejiang University-University of Edinburgh Institute, Zhejiang University, Jiaxing, 314000, China. Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310000, China. Department of Pharmacy, Taishan Hospital of Shandong Province, Taian, 271000, China. Qingdao Hiser Hospital Affiliated to Qingdao University, Qingdao, 266000, China. Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250000, China. Affiliations

刊名

Cancer science

年份

2021

ISSN

1349-7006

关键词

immune checkpoint inhibitors microbiota non-small cell lung cancer programmed death-1 progression-free survival.

摘要

Immunotherapy against cancer, through immune checkpoint inhibitors targeting the programmed death-1/programmed death-ligand 1 axis, is particularly successful in tumor by relieving the immune escape. However, inter-individual 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 patients at...更多

Immunotherapy against cancer, through immune checkpoint inhibitors targeting the programmed death-1/programmed death-ligand 1 axis, is particularly successful in tumor by relieving the immune escape. However, inter-individual 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 patients at baseline and during treatment of 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-PD-1 response. Higher gut microbiota alpha diversity indicated better response and more prolonged progression-free survival. Comparison of bacterial communities between responders and non-responders exhibited some favorable/unfavorable microbes enriched in responders/non-responders, indicating that commensal microbiota had the 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 non-responders. 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 inhibitors-based immunotherapy.收起

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