Abstract:
Microbial communities are resident to multiple niches of the human body and are important modulators of the host immune system and responses to anticancer therapies. Recent studies have shown that complex microbial communities are present within primary tumors. To investigate the presence and relevance of the microbiome in metastases, we integrated mapping and assembly-based metagenomics, genomics, transcriptomics, and clinical data of 4,160 metastatic tumor biopsies. We identified organ-specific tropisms of microbes, enrichments of anaerobic bacteria in hypoxic tumors, associations between microbial diversity and tumor-infiltrating neutrophils, and the association of Fusobacterium with resistance to immune checkpoint blockade (ICB) in lung cancer. Furthermore, longitudinal tumor sampling revealed temporal evolution of the microbial communities and identified bacteria depleted upon ICB. Together, we generated a pan-cancer resource of the metastatic tumor microbiome that may contribute to advancing treatment strategies.
摘要:
微生物群落驻留在人体的多个生态位,并且是宿主免疫系统和对抗癌疗法的反应的重要调节剂。最近的研究表明,原发性肿瘤中存在复杂的微生物群落。为了研究转移瘤中微生物组的存在和相关性,我们整合了映射和基于组装的宏基因组学,基因组学,转录组学,和4160例转移性肿瘤活检的临床资料。我们确定了微生物的器官特异性嗜性,缺氧肿瘤中厌氧菌的富集,微生物多样性与肿瘤浸润中性粒细胞之间的关联,以及肺癌中梭杆菌与免疫检查点阻断(ICB)抗性的关联。此外,纵向肿瘤采样揭示了微生物群落的时间演变,并确定了ICB耗尽的细菌。一起,我们产生了转移性肿瘤微生物组的泛癌症资源,这可能有助于推进治疗策略.