Alistipes finegoldii augments the efficacy of immunotherapy against solid tumors

Abstract

The emergence of immunotherapy has revolutionized cancer therapy. However, immunotherapeutic resistance remains a major obstacle for broader clinical application. Recent studies highlight that gut microbiota enhances immunotherapy by modulating anti-tumor immunity. In our investigation, we identify that Alistipes finegoldii (A. finegoldii) is associated with superior immunotherapy efficacy across multiple cohorts. Subsequent in vitro and in vivo experiments reveal that A. finegoldii enhances CD8⁺ T cell chemotaxis via the CXCL16-CXCR6 axis, enhancing immunotherapy efficacy. Mechanistically, a lipoprotein derived from A. finegoldii (LIPOAF) activates the nuclear factor kappa B (NF-κB) signaling pathway to augment CXCL16 expression in CCR7⁺ conventional dendritic cells through binding with the Toll-like receptor 2. Released CXCL16 subsequently facilitates the recruitment of CXCR6⁺CD8⁺ T cells into the tumor microenvironment, effectively curbing tumor growth. Our findings suggest a promising strategy for treating solid tumors by combining A. finegoldii with immunotherapy.

Keywords: Alistipes finegoldii; CXCL16; CXCR6; TLR2; anti-tumor immunity; gut microbiome; immunotherapy; lipoprotein; solid tumor.