Association of SCFA in gut microbiome and clinical response in solid cancer patients treated with andi PD 1 antibody
Abstract Background Although immunotherapy with immune checkpoint inhibitors (ICIs) has been remarkably effective across multiple cancer types. Several reports showed the gut microbiome is a possible factor proposed to impact the efficacy of ICI. The relationship between gut microbiome and immune status in tumor microenvironment remains unclear. Short chain fatty acids (SCFAs) are major end products of gut microbiota metabolites and are known to wide ranging impacts on host physiology. The objective of this study was to evaluate the fecal SCFA (fSCFA) in solid cancer patients treated with anti programmed death 1 inhibitor (PD1i) Methods This was a prospective study of patients with cancer who were treated with nivolumab (2 mg/kg, every 3 weeks; 3 mg/kg, every 2 weeks; or 240 mg/body, every 2 weeks) or pembrolizumab (200 mg/body, every 3 weeks) at Kyoto University Hospital between July 2016 and April 2018. Patients were classified into two groups: responder (R) with an objective response and non responder (NR) according to the Response Evaluation Criteria in Solid Tumors version 1.1. Fecal samples were collected before administration of PD 1 inhibitor and were analyzed by the ultra high performance liquid chromatography tandem mass spectrometry system. Results A total of 40 patients (melanoma 19; head and neck cancer 7; gastrointestinal cancer 7; genitourinary cancer 4; other 3) were enrolled. The response rate was 22.5% The fSCFAs in R patients (n 9) were significantly higher than that in NR patients (n 31) (p Conclusions The fSCFA could predict the efficacy of PD1i. Clinical trial identification UMIN000023303. Legal entity responsible for the study The authors. Funding Novartis Pharma. Disclosure M. Nomura: Research grant Funding (self) Novartis Pharma. All other authors have declared no conflicts of interest.
Annals of Oncology