Colonizable probiotic R3 enhances ICI therapy modulating PBMCs differentiation.

R3 ( R3) has been reported to be effective to improve anti-tumor therapy for anti-tumor treatment in immune checkpoint inhibitor (ICI) therapy for colorectal cancer. However, the mechanisms behind this remain unclear. The present study shows that R3 significantly enhanced anti-tumor efficacy ICI therapies in various tumor. Our results also showed the rapid adherence of R3 to intestinal epithelial cell membrane, and promoted intestinal epithelial cell expression of mucin mRNA, led to the long maintenance of R3 in colon and cecum in mice. R3 significantly elevated the levels of macrophages, CD4T cells and CD8T cells in PBMCs while simultaneously decreasing the level of programmed cell death protein 1 (PD-1) on the surface of CD4T cells and CD8T cells. In addition, indole-3-carboxaldehyde, a metabolite of R3 serves as an aryl hydrocarbon receptor (AHR) ligand regulating immune responses, was significantly upregulated in the serum of mice orally treated with R3. In summary, our findings provide novel insights into the immune regulation of probiotics in anti-tumor responses and present a potential avenue for R3 in promoting ICI efficacy.