Microbiota-driven antitumour immunity mediated by dendritic cell migration

Abstract

Gut microbiota influence the antitumour efficacy of immune checkpoint blockade^1,2,3,4,5,6, but the mechanisms of action have not been fully elucidated. Here, we show that a new strain of the bacterial genus Hominenteromicrobium (designated YB328) isolated from the faeces of patients who responded to programmed cell death 1 (PD-1) blockade augmented antitumour responses in mice. YB328 activated tumour-specific CD8⁺ T cells through the stimulation of CD103⁺CD11b⁻ conventional dendritic cells (cDCs), which, following exposure in the gut, migrated to the tumour microenvironment. Mice showed improved antitumour efficacy of PD-1 blockade when treated with faecal transplants from non-responder patients supplemented with YB238. This result suggests that YB328 could function in a dominant manner. YB328-activated CD103⁺CD11b⁻ cDCs showed prolonged engagement with tumour-specific CD8⁺ T cells and promoted PD-1 expression in these cells. Moreover, YB238-augmented antitumour efficacy of PD-1 blockade treatment was observed in multiple mouse models of cancer. Patients with elevated YB328 abundance had increased infiltration of CD103⁺CD11b⁻ cDCs in tumours and had a favourable response to PD-1 blockade therapy in various cancer types. We propose that gut microbiota enhance antitumour immunity by accelerating the maturation and migration of CD103⁺CD11b⁻ cDCs to increase the number of CD8⁺ T cells that respond to diverse tumour antigens.