Song Wencan, Liu Jizhen, Yang Jingfang, Chen Tao, Zhu Jiayi, Liu Xia
Department of Oncology, The People's Hospital of Chizhou, Chizhou, Anhui, China.
Laboratory Animal Center, Guangdong Medical University, Dongguan, Guangdong, China.
Front Microbiol. 2025 Jun 4;16:1547964. doi: 10.3389/fmicb.2025.1547964. eCollection 2025.
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.
据报道，R3在免疫检查点抑制剂（ICI）治疗结直肠癌的抗肿瘤治疗中可有效改善抗肿瘤疗效。然而，其背后的机制仍不清楚。本研究表明，R3显著增强了ICI疗法在各种肿瘤中的抗肿瘤疗效。我们的结果还显示，R3能快速黏附于肠上皮细胞膜，并促进肠上皮细胞黏蛋白mRNA的表达，使R3在小鼠结肠和盲肠中长时间维持。R3显著提高了外周血单核细胞（PBMC）中巨噬细胞、CD4T细胞和CD8T细胞的水平，同时降低了CD4T细胞和CD8T细胞表面程序性细胞死亡蛋白1（PD-1）的水平。此外，R3的代谢产物吲哚-3-甲醛作为一种调节免疫反应的芳烃受体（AHR）配体，在用R3口服治疗的小鼠血清中显著上调。总之，我们的研究结果为益生菌在抗肿瘤反应中的免疫调节提供了新的见解，并为R3提高ICI疗效提供了一条潜在途径。
