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J Thorac Oncol. 2019 Apr 23. pii: S1556-0864(19)30286-2. doi: 10.1016/j.jtho.2019.04.007. [Epub ahead of print]

The diversity of gut microbiome is associated with favorable responses to anti-PD-1 immunotherapy in Chinese non-small cell lung cancer patients.

Author information

1
Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, West Huaihai Road 241, Shanghai 200030, China.
2
Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai 201203, China.
3
Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, West Huaihai Road 241, Shanghai 200030, China; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
4
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
5
Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai 201203, China; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
6
Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, West Huaihai Road 241, Shanghai 200030, China. Electronic address: shunlu@sjtu.edu.cn.

Abstract

PURPOSE:

Gut microbiome affecting the responses to immune checkpoint inhibitors (ICIs) against advanced non-small cell lung cancer (NSCLC) has been investigated in western population. However, considering preexisting genetic and gut microbiota variation, the relevance remains unknown in east-Asian NSCLC population. The study is designed to explore the relationship between gut microbiome and clinical outcomes in Chinese NSCLC patients treated with an anti-PD-1 blockade.

METHODS:

37 advanced NSCLC patients receiving the treatment of nivolumab were enrolled in the study from the clinical trials CheckMate 078 (NCT02613507) and CheckMate 870 (NCT03195491). Fecal samples were collected at the starting point, every time point receiving nivolumab as well as clinical evaluation and that with disease progression. 16S ribosome RNA gene sequencing was applied to assess gut microbiota profiles. Peripheral immune signatures were determined by multi-color flow cytometry in parallel.

RESULTS:

When subgrouping patients into responder (R) and non-responder (NR) according to the clinical response assessed by RECIST1.1, R patients harbored higher diversity of gut microbiome at the starting point with stable composition during the treatment. Patients with high microbiome diversity had significantly prolonged progression-free survival (PFS) when compared to those with low diversity. Compositional difference was observed between two groups as well with the enrichment of Alistipes putredinis, Bifidobacterium longum, Prevotella copri in R whereas Ruminococcus_unclassified in NR. Analysis of systemic immune responses using multi-color flow cytometry revealed that patients with high abundance of microbiome diversity in the gut had more frequencies of unique memory CD8+ T cell and NK cell subsets in the periphery in response to anti-PD-1 therapy.

CONCLUSIONS:

Our results reveal strong correlation between gut microbiome diversity and the responses to anti-PD-1 immunotherapy in Chinese advanced NSCLC patients. Patients with favorable gut microbiome (such as high diversity) exhibit enhanced memory T cell and NK cell signatures in the periphery. These findings provide important implications for the prediction and the evaluation of anti-PD-1 immunotherapy against NSCLC in Chinese population.

KEYWORDS:

Advanced non-small cell lung cancer; clinical benefit; gut microbiota; nivolumab; systemic immune signatures

PMID:
31026576
DOI:
10.1016/j.jtho.2019.04.007

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