RX-Af01 augments the efficacy of immunotherapy against solid tumors (PRJCA028809)

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 can enhance immunotherapy efficacy by modulating various aspects of the anti-tumor immune response. In our investigation, we identify that Alistipes finegoldii (A. finegoldii) is associated with superior immunotherapy efficacy in multiple cohorts. Subsequent in vitro and in vivo experiments reveal that A. finegoldii enhances CD8+ T cell chemotaxis via the CXCL16-CXCR6 axis, thereby potentiating the efficacy of immunotherapy. Mechanistically, a lipoprotein derived from A. finegoldii (LIPOAF) activates the NF-?B signaling pathway to augment CXCL16 expression in CCR7+ conventional dendritic cells through binding with the TLR2 receptor. Released CXCL16 subsequently facilitates the recruitment of CXCR6+CD8+ T cells into the tumor microenvironment, effectively curbing tumor growth. Our findings suggest a promising approach to cancer treatment by combining A. finegoldii with immunotherapy in solid tumors.