Single-cell transcriptomic analysis reveals gut microbiota-immunotherapy synergy through modulating tumor microenvironment

Abstract The gut microbiota crucially regulates the efficacy of immune checkpoint inhibitor (ICI) based immunotherapy, but the underlying mechanisms remain unclear at the single-cell resolution. Using single-cell RNA sequencing and subsequent validations, we investigate gut microbiota-ICI synergy by profiling the tumor microenvironment (TME) and elucidating critical cellular interactions in mouse models. Our findings reveal that intact gut microbiota combined with ICIs may synergistically increase the proportions of CD8 + , CD4 + , and γδ T cells, reduce glycolysis metabolism, and reverse exhausted CD8 + T cells into memory/effector CD8 + T cells, enhancing antitumor response. This synergistic effect also…

• NN
  National Natural Science Foundation of China

  Awards: 82273445, 2021YFA1301200
• CP
  China Postdoctoral Science Foundation
• SU
  Sichuan University
• WC
  West China Hospital, Sichuan University

  Awards: ZYYC23025, 1.3.5