德克萨斯大学Susan Bullman研究团队近日取得一项新成果。经过不懈努力，他们揭示了肿瘤浸润细菌破坏癌上皮细胞的相互作用并诱导细胞周期阻滞。相关论文于2025年10月16日发表于国际顶尖学术期刊《癌细胞》杂志上。

该课题组研究人员描述了细胞外肿瘤内细菌，包括热杆菌，调节癌症上皮细胞行为的机制。空间成像和单细胞空间转录组学显示，这些细菌主要定位于结直肠癌和口腔癌的肿瘤微生境内的细胞外，其特征是细胞密度、转录活性和增殖降低。体外，有核热杆菌破坏上皮接触，诱导G0-G1阻滞和转录静止。这种状态赋予5-氟耐药并重塑肿瘤微环境。研究结果通过活细胞成像、空间分析、motheme模型和52例结直肠癌患者队列验证。转录组学揭示了细菌富集区细胞周期、转录和抗原呈递基因的下调，与静止、免疫逃避表型一致。在一个独立的直肠癌队列中，高热杆菌负担与治疗反应降低相关。这些结果将细胞外细菌与癌细胞静止和化疗耐药联系起来，突出了微生物-肿瘤相互作用作为治疗靶点。

研究人员表示，肿瘤浸润细菌越来越被认为是癌症进展和治疗耐药性的调节剂。

附：英文原文

Title: Tumor-infiltrating bacteria disrupt cancer epithelial cell interactions and induce cell-cycle arrest

Author: Jorge Luis Galeano Nio, Falk Ponath, Victor A. Ajisafe, Clara R. Becker, Andrew G. Kempchinsky, Martha A. Zepeda-Rivera, Javier A. Gomez, Hanrui Wu, Jessica G. Terrazas, Heather Bouzek, Elizabeth Cromwell, Pritha Chanana, Matthew Wong, Ashish Damania, Michael G. White, Y. Nancy You, Scott Kopetz, Nadim J. Ajami, Jennifer A. Wargo, Christopher D. Johnston, Susan Bullman

Issue&Volume: 2025-10-16

Abstract: Tumor-infiltrating bacteria are increasingly recognized as modulators of cancer progression and therapy resistance. We describe a mechanism by which extracellular intratumoral bacteria, including Fusobacterium, modulate cancer epithelial cell behavior. Spatial imaging and single-cell spatial transcriptomics show that these bacteria predominantly localize extracellularly within tumor microniches of colorectal and oral cancers, characterized by reduced cell density, transcriptional activity, and proliferation. In vitro, Fusobacterium nucleatum disrupts epithelial contacts, inducing G0-G1 arrest and transcriptional quiescence. This state confers 5-fluorouracil resistance and remodels the tumor microenvironment. Findings were validated by live-cell imaging, spatial profiling, mouse models, and a 52-patient colorectal cancer cohort. Transcriptomics reveals downregulation of cell cycle, transcription, and antigen presentation genes in bacteria-enriched regions, consistent with a quiescent, immune-evasive phenotype. In an independent rectal cancer cohort, high Fusobacterium burden correlates with reduced therapy response. These results link extracellular bacteria to cancer cell quiescence and chemoresistance, highlighting microbial-tumor interactions as therapeutic targets.

DOI: 10.1016/j.ccell.2025.09.010

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00402-7