Xu Song, Kong Jianqiao, Dai Yang, Li Hengping
Department of General Surgery, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China.
Turk J Gastroenterol. 2024 Nov 28;35(12):909-921. doi: 10.5152/tjg.2024.23683.
BACKGROUND/AIMS: Colorectal cancer (CRC) stands as the third most prevalent cancer on a global scale. In recent years, immunotherapy, such as anti-PD-L1 treatment, has demonstrated promising therapeutic outcomes in CRC. However, studies have suggested that intestinal microbiota may influence the efficacy of anti-PD-L1 immunotherapy. This study aimed to investigate the linkage between intestinal bacteria and anti-PD-L1 therapy.
Bioinformatics analysis was employed to study the correlation between the intestinal microbiota of CRC patients and immune infiltration. The study delved into the relationship between Prevotellaceae and immune-related genes in CRC. Mouse experiments were conducted to validate the association between Prevotellaceae abundance and the efficacy of anti-PD-L1 tumor treatment. Prevotellaceae abundance in mouse feces was assayed by 16S sequencing. Flow cytometry was utilized to assay immune cell infiltration in patient tumor tissues, while western blot and quantitative polymerase chain reaction (qPCR) assays measured IFN-γ, IL-2, and PD-L1 levels in tumor tissues.
The high immune cell infiltration group demonstrated reduced tumor purity when compared with the group displaying low immune cell infiltration. Substantial variances were discerned in the Stromal Score, Immune Score, ESTIMATE Score, and Tumor Purity among the 3 distinct subtypes. The community evenness in the gut microbiota of CRC patients from cluster 2 and cluster 3 subtypes displayed significant differences. Members of the Prevotellaceae family were significantly enriched in the gut microbiota of cluster 3 subtype patients. In vivo experiments ascertained the supportive role of Prevotellaceae in anti-PD-L1 immunotherapy.
The facilitating effect of Prevotellaceae on anti-PD-L1 treatment was demonstrated in CRC. The findings suggest that elevating Prevotellaceae abundance may offer a new direction for assisting in CRC immunotherapy and provide a foundation for devising more effective CRC immunotherapeutic strategies.
背景/目的：结直肠癌（CRC）是全球第三大常见癌症。近年来，免疫疗法，如抗程序性死亡受体配体1（PD-L1）治疗，在结直肠癌中显示出有前景的治疗效果。然而，研究表明肠道微生物群可能会影响抗PD-L1免疫疗法的疗效。本研究旨在探讨肠道细菌与抗PD-L1治疗之间的联系。
采用生物信息学分析研究结直肠癌患者肠道微生物群与免疫浸润之间的相关性。该研究深入探讨了普雷沃氏菌科与结直肠癌中免疫相关基因之间的关系。进行小鼠实验以验证普雷沃氏菌科丰度与抗PD-L1肿瘤治疗疗效之间的关联。通过16S测序测定小鼠粪便中普雷沃氏菌科的丰度。利用流式细胞术测定患者肿瘤组织中的免疫细胞浸润情况，而蛋白质免疫印迹法和定量聚合酶链反应（qPCR）测定肿瘤组织中干扰素-γ（IFN-γ）、白细胞介素-2（IL-2）和PD-L1的水平。
与免疫细胞浸润低的组相比，免疫细胞浸润高的组肿瘤纯度降低。在3种不同亚型之间，基质评分、免疫评分、ESTIMATE评分和肿瘤纯度存在显著差异。2型和3型亚型的结直肠癌患者肠道微生物群的群落均匀度显示出显著差异。普雷沃氏菌科成员在3型亚型患者的肠道微生物群中显著富集。体内实验确定了普雷沃氏菌科在抗PD-L1免疫治疗中的支持作用。
在结直肠癌中证实了普雷沃氏菌科对抗PD-L1治疗的促进作用。研究结果表明，提高普雷沃氏菌科丰度可能为辅助结直肠癌免疫治疗提供新方向，并为制定更有效的结直肠癌免疫治疗策略提供依据。
