Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China; Research Center for Biliary Disease, West China Hospital of Sichuan University, Chengdu, China.
Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Neoplasia. 2023 Sep;43:100920. doi: 10.1016/j.neo.2023.100920. Epub 2023 Jul 27.
Most patients with resected bile tract cancers (BTCs) survive for less than 5 years; however, some achieve better prognosis. The tumor microbiome can improve survival by regulating the tumor immune microenvironment. However, whether the tumor microbiome promotes immune cell infiltration in BTCs is unknown. This study aimed to determine the association between CD8 T lymphocyte infiltration and the tumor microbiome in patients with resected BTCs.
Archived formalin-fixed paraffin-embedded tumor specimens were collected from patients with resected BTCs and analyzed using 16S rRNA gene sequencing to identify that prognosis-related and significantly differentially enriched taxa. Gene ontology (GO) analysis of the differentially enriched taxa was used to assess how CD8 T lymphocyte infiltration is affected by the tumor microbiome of BTCs.
We enrolled 32 patients with resected BTCs. The high CD8 lymphocyte-infiltration (CD8) group had four significantly enriched taxa, and in the low CD8 lymphocyte-infiltration (CD8) group comprised one significantly enriched taxon. Patients with higher Clostridia abundance (enriched in the CD8 group) experienced longer overall survival than those with lower abundance. The enrichment of Clostridia in the CD8 group corresponded with lower CCL2 expression and downregulation of phosphatidylinositol 3-kinase activity, which might decrease myeloid-derived suppressor cell recruitment to the tumor milieu, thus increasing CD8 lymphocyte infiltration in BTCs.
The tumor microbiome is related to CD8 T lymphocyte infiltration in patients with resected BTCs. The relationship between tumor Clostridia and high infiltration of CD8 T lymphocytes might reflect decreased recruitment of myeloid-derived suppressor cells via the PI3K-CCL2-CCR2 axis.
大多数接受胆管癌（BTC）切除术的患者存活时间不到 5 年；然而，一些患者预后较好。肿瘤微生物组可以通过调节肿瘤免疫微环境来提高生存率。然而，肿瘤微生物组是否促进 BTC 中免疫细胞浸润尚不清楚。本研究旨在确定切除的 BTC 患者中 CD8 T 淋巴细胞浸润与肿瘤微生物组之间的关联。
从接受 BTC 切除术的患者中收集存档的福尔马林固定石蜡包埋肿瘤标本，并使用 16S rRNA 基因测序进行分析，以确定与预后相关且显著差异富集的分类群。对差异富集分类群进行基因本体（GO）分析，以评估 BTC 肿瘤微生物组如何影响 CD8 T 淋巴细胞浸润。
我们纳入了 32 名接受 BTC 切除术的患者。高 CD8 淋巴细胞浸润（CD8）组有四个显著富集的分类群，而在低 CD8 淋巴细胞浸润（CD8）组中有一个显著富集的分类群。Clostridia 丰度较高（在 CD8 组中富集）的患者总生存期较长，而丰度较低的患者总生存期较短。CD8 组中 Clostridia 的富集与 CCL2 表达降低和磷脂酰肌醇 3-激酶活性下调相对应，这可能会减少髓系来源的抑制细胞募集到肿瘤微环境中，从而增加 BTC 中的 CD8 T 淋巴细胞浸润。
肿瘤微生物组与切除的 BTC 患者中 CD8 T 淋巴细胞浸润有关。肿瘤梭菌与 CD8 T 淋巴细胞高浸润之间的关系可能反映了通过 PI3K-CCL2-CCR2 轴减少髓系来源的抑制细胞的募集。
