Content area
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.
MethodsFecal 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.
ResultsWe 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.
ConclusionsThe α-diversity of gut microbiota is positively correlated with more prolonged overall survival in cancer patients following ICI therapy.
Details
1 Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan; Immuno-Oncology Center of Excellence, Chang Gung Memorial Hospital, Taoyuan, Taiwan
2 Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
3 School of Medicine, Chang Gung University College of Medicine, Taoyuan, Taiwan
4 Immuno-Oncology Center of Excellence, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Nursing, Chang Gung Memorial Hospital, Taoyuan, Taiwan
5 Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Microbiology and Immunology, Chang Gung University College of Medicine, Taoyuan, Taiwan
6 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
7 Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan
8 Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan