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食管鳞状细胞癌中肠道微生物双歧杆菌与抗肿瘤免疫应答的关系

英文原题:The Relationship Between Gut Microbiome Bifidobacterium and Anti-tumor Immune Responses in Esophageal Squamous Cell Carcinoma.

PubMed 2025/03/04(内容时间) Ann Surg Oncol Q1 · IF 3.8(JCR 2025)

研究概要

双歧杆菌可以诱导上调抗肿瘤免疫反应,并且在营养状况良好的病例中更为普遍。

研究思路结论见上方概要

双歧杆菌属是胃肠道中一种重要的细菌群体。先前的研究结果表明,在小鼠黑色素瘤模型中,双歧杆菌与肿瘤抑制有关。此外,当与程序性死亡配体1(PD-L1)抗体联合使用时,它可以通过增加肿瘤特异性T细胞反应和促进抗原特异性T细胞浸润到肿瘤中,来增强抗肿瘤治疗效果。然而,在食管鳞状细胞癌(ESCC)中缺乏关于双歧杆菌的研究。本研究旨在探讨双歧杆菌对这种癌症类型的潜在影响。

我们检测了213例接受肿瘤切除术的ESCC患者样本。通过定量聚合酶链反应和荧光原位杂交(FISH)确认了双歧杆菌的存在。分析了双歧杆菌阳性与患者总生存期(OS)的关系。通过苏木精-伊红染色评估TIL(肿瘤浸润淋巴细胞)(TILs),并使用免疫组织化学评估程序性死亡-1(PD-1)、PD-L1、分化簇8(CD8)和叉头框P3(FOXP3)的表达。通过计算机断层扫描评估营养状态。

双歧杆菌阳性与患者OS或TIL水平无相关性;然而,正常组织中的双歧杆菌阳性与较低的FOXP3水平相关,提示其可能在上调抗肿瘤免疫反应中发挥作用。瘤周正常组织中存在双歧杆菌的患者表现出更好的骨骼肌面积和体积。相反,肿瘤组织中双歧杆菌阳性与较差的预后营养指数值相关,可能是由于白蛋白水平降低所致。

展开英文摘要原文

BACKGROUND: The Bifidobacterium genus is a prominent bacterial population in the gastrointestinal tract. Previous findings suggest that Bifidobacterium is linked to tumor suppression in mouse models of melanoma. Additionally, when combined with the programmed death-ligand 1 (PD-L1) antibody, it can enhance anti-tumor treatment by increasing tumor-specific T-cell responses and promoting infiltration of antigen-specific T cells into tumors. However, there is a lack of studies on Bifidobacterium in esophageal squamous cell carcinoma (ESCC). This study aimed to investigate the potential impact of Bifidobacterium on this cancer type. METHODS: We examined 213 samples from ESCC patients who underwent tumor resection. The presence of Bifidobacterium was confirmed using quantitative polymerase chain reaction and fluorescent in situ hybridization (FISH). Patient overall survival (OS) was analyzed with Bifidobacterium positivity. Tumor-infiltrating lymphocytes (TILs) were evaluated via hematoxylin and eosin stains, and immunohistochemistry was used to assess programmed death-1 (PD-1), PD-L1, cluster of differentiation 8 (CD8), and forkhead box P3 (FOXP3) expression. Nutritional status was evaluated via computed tomography scans. RESULTS: Bifidobacterium positivity showed no correlation with patient OS or TIL levels; however, Bifidobacterium positivity in normal tissue was associated with lower FOXP3 levels, suggesting a potential role in upregulating anti-tumor immune responses. Patients with Bifidobacterium present in peritumor normal tissue exhibited better skeletal muscle area and volume. Conversely, Bifidobacterium positivity in tumor tissue was associated with poorer prognostic nutrition index values, likely due to decreased albumin levels. CONCLUSION: Bifidobacterium can induce the upregulated anti-tumor immune response and is more prevalent in cases with good nutritional status.

论文信息

作者
Wang H、Baba Y、Hara Y、Toihata T、Kosumi K、Harada K、Iwatsuki M、Miyamoto Y
第一作者单位
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.Japan
通讯作者单位
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. y-baba@kumamoto-u.ac.jp.Japan
期刊
Annals of surgical oncology2025 May
原文标识
PubMed 40035906 · DOI 10.1245/s10434-024-16288-4