Molecular Oncology, PSL Research University, CNRS, UMR 144, Institut Curie, Paris 75005, France; Paris Center for Microbiome Medicine, Fédération Hospitalo-Universitaire, Paris, France; Medical Oncology Department, Institut Curie, Saint-Cloud 92210, France.
Department of Drug Development and Innovation (D3i), Institut Curie, Paris-Saclay University, Paris, France.
Eur J Cancer. 2023 Apr;183:152-161. doi: 10.1016/j.ejca.2023.01.024. Epub 2023 Feb 8.
Data on the role of the microbiota in cancer have accumulated in recent years, with particular interest in intratumoral bacteria. Previous results have shown that the composition of intratumoral microbiome is different depending on the type of primary tumour and that bacteria from the primary tumour could migrate to metastatic sites.
Seventy-nine patients with breast, lung, or colorectal cancer and available biopsy samples from lymph node, lung, or liver site, treated in the SHIVA01 trial were analysed. We performed bacterial 16S rRNA gene sequencing on these samples to characterise the intratumoral microbiome. We assessed the association between microbiome composition, clinicopathological characteristics, and outcomes.
Microbial richness (Chao1 index), evenness (Shannon index) and beta-diversity (Bray Curtis distance) were associated with biopsy site (p = 0.0001, p = 0.03 and p < 0.0001, respectively) but not with primary tumour type (p = 0.52, p = 0.54 and p = 0.82, respectively). Furthermore, microbial richness was inversely associated with tumour-infiltrating lymphocytes (TILs, p = 0.02), and PD-L1 expression on immune cells (p = 0.03), or assessed by Tumor Proportion Score (TPS, p = 0.02) or Combined Positive Score (CPS, p = 0.04). Beta-diversity was also associated with these parameters (p < 0.05). Patients with lower intratumoral microbiome richness had shorter overall survival (p = 0.03) and progression-free survival (p = 0.02) in multivariate analysis.
Biopsy site, rather than primary tumour type, was strongly associated with microbiome diversity. Immune histopathological parameters such as PD-L1 expression and TILs were significantly associated with alpha and beta-diversity supporting the cancer-microbiome-immune axis hypothesis.
近年来，关于微生物组在癌症中的作用的数据不断积累，尤其是对肿瘤内细菌的研究兴趣不断增加。先前的研究结果表明，肿瘤内微生物组的组成因原发肿瘤的类型而异，并且原发肿瘤的细菌可以迁移到转移部位。
对 SHIVA01 试验中 79 例患有乳腺癌、肺癌或结直肠癌且有来自淋巴结、肺或肝部位活检样本的患者进行分析。我们对这些样本进行了细菌 16S rRNA 基因测序，以描述肿瘤内微生物组。我们评估了微生物组组成与临床病理特征和结局之间的关联。
微生物丰富度（Chao1 指数）、均匀度（Shannon 指数）和β多样性（Bray Curtis 距离）与活检部位相关（p=0.0001、p=0.03 和 p<0.0001），但与原发肿瘤类型无关（p=0.52、p=0.54 和 p=0.82）。此外，微生物丰富度与肿瘤浸润淋巴细胞（TILs，p=0.02）和免疫细胞上的 PD-L1 表达（p=0.03）或通过肿瘤比例评分（TPS，p=0.02）或综合阳性评分（CPS，p=0.04）评估的 PD-L1 表达呈负相关。β多样性也与这些参数相关（p<0.05）。在多变量分析中，肿瘤内微生物丰富度较低的患者总生存期（p=0.03）和无进展生存期（p=0.02）较短。
活检部位而不是原发肿瘤类型与微生物组多样性密切相关。免疫组织病理学参数，如 PD-L1 表达和 TILs，与α和β多样性显著相关，支持癌症-微生物组-免疫轴假说。
