Association of Short-Chain Fatty Acids in the Gut Microbiome With Clinical Response to Treatment With Nivolumab or Pembrolizumab in Patients With Solid Cancer Tumors

• DOI: 10.1001/jamanetworkopen.2020.2895
• Publication Date: 2020-04-16T18:31:01Z
• Authors: Motoo Nomura; Ryosuke Nagatomo; Keitaro Doi; Juko Shimizu; Kiichiro Baba; Tomoki Saito; Shigemi Matsumoto; Koichi Inoue; Manabu Muto
• Keywords: Immune checkpoint

<h3>Importance</h3> Immunotherapy using immune checkpoint inhibitors has been remarkably effective for treating multiple cancer types, and the gut microbiome is a possible factor affecting inhibitor efficacy. However, association between status of tumor microenvironment remains unclear. Short-chain fatty acids (SCFAs) are major end product metabolites produced by microbiota have wide-ranging impacts on host physiology. <h3>Objective</h3> To evaluate fecal plasma SCFAs in patients with solid tumors treated programmed cell death-1 (PD-1i). <h3>Design, Setting, Participants</h3> This was prospective cohort biomarker study who planned therapy PD-1i at Kyoto University Hospital July 2016 February 2019. Data were analyzed from October 2019 to 2020. <h3>Exposures</h3> Patients nivolumab or pembrolizumab classified into 2 groups based their treatment response Response Evaluation Criteria Solid Tumors version 1.1: responders achieved an objective nonresponders. Dietary information terms intake frequency obtained. Concentrations samples collected before administration measured ultra-high-performance liquid chromatography coupled tandem mass spectrometry. <h3>Main Outcomes Measures</h3> The concentration progression-free survival. <h3>Results</h3> Among 52 enrolled, median (range) patient age 67 (27-84) years, 23 (44%) women. Median duration follow-up survivors after 2.0 (0.4–4.1) years. overall rate 28.8%. High concentrations some associated longer These included acetic acid (hazard ratio [HR], 0.29; 95% CI, 0.15-0.54), propionic (HR, 0.08; 0.03-0.20), butyric 0.31; 0.16-0.60), valeric 0.53; 0.29-0.98), isovaleric 0.38; 0.14-0.99). <h3>Conclusions Relevance</h3> Results this suggest that SCFA may efficacy; thus, be link Because examinations completely noninvasive, they applicable routine monitoring patients.