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Gut microbiota and clinical response to immune checkpoint inhibitor therapy in patients with advanced cancer
John Wen‐Cheng Chang (Chang Gung University, Chang Gung Memorial Hospital), Jia‐Juan Hsieh (Chang Gung University, Chang Gung Memorial Hospital), Chih-Yu Tsai (Chang Gung University, Chang Gung Memorial Hospital), Horng-Yih Chiu (Chang Gung University), Yu-Feng Lin (Chang Gung Memorial Hospital, Taoyuan Chang Gung Memorial Hospital), Chiao‐En Wu (Chang Gung University, Chang Gung Memorial Hospital), Yung‐Chi Shen (Chang Gung University, Chang Gung Memorial Hospital), Ming‐Mo Hou (Chang Gung University, Chang Gung Memorial Hospital), Chieh-Ying Chang (Chang Gung University, Chang Gung Memorial Hospital), Jian-An Chen (Chang Gung University, Chang Gung Memorial Hospital), Chyi‐Liang Chen (Chang Gung University, Chang Gung Memorial Hospital), Cheng‐Tang Chiu (Chang Gung Memorial Hospital, Taoyuan Chang Gung Memorial Hospital), Yuan‐Ming Yeh (Chang Gung University of Science and Technology, Chang Gung Memorial Hospital), Cheng-Hsun Chiu (Chang Gung Memorial Hospital, Taoyuan Chang Gung Memorial Hospital)
Abstract: BACKGROUND: There is currently no well-accepted consensus on the association between gut microbiota and the response to treatment of immune checkpoint inhibitors (ICIs) in patients with advanced cancer. METHODS: Fecal samples were collected before ICI treatment. Gut microbiota was analyzed using 16 S ribosomal RNA sequencing. We investigated the relationship between the α-diversity of fecal microbiota and patients' clinical outcomes. Microbiota profiles from patients and healthy controls were determined. Pre-treatment serum was examined by cytokine array. RESULTS: We analyzed 74 patients, including 42 with melanoma, 8 with kidney cancer, 13 with lung cancer, and 11 with other cancers. Combination therapy of anti-PD1 and anti-CTLA-4 was used in 14 patients, and monotherapy in the rest. Clinical benefit was observed in 35 (47.3 %) cases, including 2 complete responses, 16 partial responses, and 17 stable diseases according to RECIST criteria. No significant difference in α-diversity was found between the benefiter and non-benefiter groups. However, patients with α-diversity within the range of our healthy control had a significantly longer median overall survival (18.9 months), compared to the abnormal group (8.2 months) (p = 0.041, hazard ratio = 0.546) for all patients. The microbiota composition of the benefiters was similar to that of healthy individuals. Furthermore, specific bacteria, such as Prevotella copri and Faecalibacterium prausnitzii, were associated with a favorable outcome. We also observed that serum IL-18 before treatment was significantly lower in the benefiters, compared to non-benefiters. CONCLUSIONS: The α-diversity of gut microbiota is positively correlated with more prolonged overall survival in cancer patients following ICI therapy.