Emerging evidence indicates that gut microbiota dysbiosis markedly compromises the efficacy of lung cancer immunotherapy. In our study, superparamagnetic iron oxide nanoparticle assemblies (SPIOCAs) were developed and shown to effectively inhibit lung cancer growth at a dose of 12.5 mg/kg. Pretreatment with broad-spectrum antibiotics aggravates the gut dysbiosis that blunts programmed cell death protein 1 (PD-1) blockade in tumor-bearing mice, whereas SPIOCA administration reconstituted the gut microbiota and thereby resensitized tumors to anti-PD-1 therapy. SPIOCA gavage fortified intestinal barrier integrity—evidenced by elevated ZO-1, ZO-2, Occludin and Claudin-1 expression—and potentiated antitumor immune-cell infiltration, specifically by CD8+ T cells and dendritic cells, into the tumor microenvironment. We therefore preliminarily conclude that SPIOCAs restore gut microbiota homeostasis in lung cancer, thereby enhancing intestinal barrier integrity and converting the tumor immune microenvironment from an immune desert to an immune-inflamed phenotype, ultimately improving lung cancer immunotherapy efficacy.
新近证据表明，肠道菌群失调会显著削弱肺癌免疫治疗的疗效。本研究开发了超顺磁性氧化铁纳米颗粒组装体（SPIOCAs），并证明其在12.5 mg/kg剂量下能有效抑制肺癌生长。广谱抗生素预处理会加剧荷瘤小鼠的肠道菌群失调，从而削弱程序性细胞死亡蛋白1（PD-1）阻断效果；而给予SPIOCAs可重建肠道菌群，使肿瘤恢复对抗PD-1治疗的敏感性。灌胃SPIOCAs能增强肠道屏障完整性——表现为ZO-1、ZO-2、Occludin和Claudin-1表达升高，并促进抗肿瘤免疫细胞（特别是CD8+ T细胞和树突状细胞）向肿瘤微环境浸润。因此我们初步认为，SPIOCAs可通过恢复肺癌中的肠道菌群稳态，增强肠道屏障完整性，并将肿瘤免疫微环境从免疫荒漠状态转化为免疫炎症表型，最终提升肺癌免疫治疗效果。
肿瘤(癌症)患者之家