ABSTRACT
Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.
Subject(s)
Gastrointestinal Microbiome/immunology , Immunotherapy , Melanoma/therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Skin Neoplasms/therapy , Animals , Fecal Microbiota Transplantation , Gastrointestinal Microbiome/genetics , Humans , Melanoma/immunology , Metagenome , Mice , Skin Neoplasms/immunologyABSTRACT
Numerous studies have been conducted on swimmer's itch, but very few have been in Montana and none on Flathead Lake, the largest, natural freshwater lake in the western United States. We conducted a study to determine the prevalence of hosts transmitting cercariae causing swimmer's itch in this lake. Hosts for this life cycle were determined by direct observation of fresh waterfowl fecal material for the presence of miracidia, and snails for the presence of cercariae. Swimmer's itch-producing cercariae were verified directly by placing various species on the arms of human volunteers and waiting for a reaction. Results of the study were further substantiated using a controlled experiment in which snails were individually infected with miracidia from the suspected waterfowl host and then checked for infection after a 6-wk incubation period. Our findings show that the common merganser (Mergus merganser) and the snail Stagnicola elrodi were natural hosts of the swimmer's itch parasite (Trichobiharzia ocellata) with prevalences of 84% and 2.0%, respectively. To our knowledge this is the first documented case of S. elrodi transmitting the swimmer's itch cercariae.
