High Bacterial Abundances of Doreaand Pediococcusin the Gut Microbiome Linked to Expansion, Immune Checkpoint Expression and Efficacy of CD19-Directed CAR T-Cells in Patients with r/r DLBCL

Introduction: The crosstalk of the gut microbiome and the human host can influence T-cell immune responses and has emerged as a modulator in cancer immunotherapy (Gopalakrishnan et al., 2018). Individual bacteria isolated from human fecal specimen were also shown to shape systemic and gut mucosal T cell repertoires (Geva-Zatorsky et al., 2017), and several commensal members of the human gut microbiome were recently associated with the kinetics of the reconstitution of peripheral immune cells after allo-HCT (Schluter et al., 2020). However, in patients treated with CAR T-cells a link between gut microbiome configurations and T-cell characteristics has not been described yet. Recently, we and others could associate low CAR T-cell expansion and dysfunction with treatment failure. Here, we hypothesize that certain gut microbes or even intestinal monodomination of facultative pathogens may correlate with CAR T-cell expansion and expression profile of immune checkpoint molecules which might impact treatment outcome.