Thoracic and GI Malignancies Branch, National Cancer Institute, Bethesda, Maryland, USA.
Lymphocyte Biology Section, Laboratory of Immune System Biology, NIAID, Bethesda, Maryland, USA.
J Immunother Cancer. 2022 Jul;10(7). doi: 10.1136/jitc-2022-004698.
The lung intratumor microbiome influences lung cancer tumorigenesis and treatment responses, but detailed data on the extent, location, and effects of microbes within lung tumors are missing, information needed for improved prognosis and treatment.
To address this gap, we developed a novel spatial meta-transcriptomic method simultaneously detecting the expression level of 1,811 host genes and 3 microbe targets (bacteria, fungi, and cytomegalovirus). After rigorous validation, we analyzed the spatial meta-transcriptomic profiles of tumor cells, T cells, macrophages, other immune cells, and stroma in surgically resected tumor samples from 12 patients with early-stage lung cancer.
Bacterial burden was significantly higher in tumor cells compared with T cells, macrophages, other immune cells, and stroma. This burden increased from tumor-adjacent normal lung and tertiary lymphoid structures to tumor cells to the airways, suggesting that lung intratumor bacteria derive from the latter route of entry. Expression of oncogenic β-catenin was strongly correlated with bacterial burden, as were tumor histological subtypes and environmental factors.
Intratumor bacteria were enriched with tumor cells and associated with multiple oncogenic pathways, supporting a rationale for reducing the local intratumor microbiome in lung cancer for patient benefit.
NCT00242723, NCT02146170.
肺部肿瘤内的微生物组会影响肺癌的发生和治疗反应，但对于肺部肿瘤内微生物的范围、位置和影响的详细数据仍不清楚，这些信息对于改善预后和治疗至关重要。
为了弥补这一空白，我们开发了一种新颖的空间宏转录组学方法，同时检测了 1811 个宿主基因和 3 个微生物靶标（细菌、真菌和巨细胞病毒）的表达水平。经过严格验证后，我们分析了 12 名早期肺癌患者手术切除肿瘤样本中肿瘤细胞、T 细胞、巨噬细胞、其他免疫细胞和基质的空间宏转录组谱。
与 T 细胞、巨噬细胞、其他免疫细胞和基质相比，肿瘤细胞中的细菌负担明显更高。这种负担从肿瘤旁正常肺和三级淋巴结构增加到肿瘤细胞，再到气道，表明肺内肿瘤细菌来源于后一种进入途径。致癌 β-连环蛋白的表达与细菌负担强烈相关，肿瘤组织学亚型和环境因素也是如此。
肿瘤内细菌在肿瘤细胞中富集，并与多种致癌途径相关，支持在肺癌患者中减少局部肿瘤内微生物组以获益的原理。
NCT00242723，NCT02146170。
