FMT converts cancer immunotherapy non-responders to responders
Adding fecal microbiota transplantation to treatment in patients with programmed cell death protein 1 melanoma altered the gut microbiome and reprogrammed tumor microenvironment to overcome resistance to anti-programmed cell death protein 1 therapy, according to study results.
“Our findings warrant further investigation in larger clinical trials to better identify microbial, circulating and intra-tumoral biomarkers to select patients most likely to benefit from microbiome-based therapy of melanoma,” Diwakar Davar, MD, from the department of medicine, University of Pittsburgh Medical Center, Hillman Cancer Center, University of Pittsburgh, and colleagues wrote. “We expect that such studies will lead to the identification of a bacterial consortium capable of converting a subset of melanoma patients primary refractory to anti–PD-1 therapy into[responder] patients.”
Between June 2018 and January 2020, Davar and colleagues evaluated safety and efficacy of responder-derived FMT in combination with anti-programmed cell death protein 1 (anti-PD-1) in 16 patients with PD-1 refractory melanoma. Serial stool sampling and extensive infectious studies to eliminate the possibility of transmitting infectious agents were performed in all patients and candidate donors.
According to researchers, administration of FMT initiated donor bacteria-specific immunoglobulin G to a great extent in responders vs. no responders, which demonstrated successful implantation and mucosal translocation was more likely to occur in responders.
Results showed the combination therapy provided clinical benefit in six of 15 patients. Investigators noted the combination induced rapid and durable microbiota perturbation. Recipient serum and donor feces was used to assess humoral immune response to donor bacteria.
“Responders exhibited increased abundance of taxa that were previously shown to be associated with CD8+ response to anti–PD-1, increased T cell activation, and decreased frequency of interleukin-8 expressing myeloid cells,” Davar and colleagues wrote. “Responders had distinct proteomic and metabolomic signatures, and trans kingdom network analyses confirmed that the gut microbiome regulated these changes.”