肠道癌微生物标志物（GOMS）作为癌症免疫治疗的下一代生物标记物

SCI

10 July 2023

Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy

(Nature Reviews Clinical Oncology, IF: 78.8)

Andrew Maltez Thomas, Marine Fidelle, Bertrand Routy, Guido Kroemer, Jennifer A. Wargo, Nicola Segata, Laurence Zitvogel

CORRESPONDENCE TO: laurence.zitvogel@gustaveroussy.fr

Abstract 摘要

Oncogenesis is associated with intestinal dysbiosis, and stool shotgun metagenomic sequencing in individuals with this condition might constitute a non-invasive approach for the early diagnosis of several cancer types. The prognostic relevance of antibiotic intake and gut microbiota composition urged investigators to develop tools for the detection of intestinal dysbiosis to enable patient stratification and microbiota-centred clinical interventions. Moreover, since the advent of immune-checkpoint inhibitors (ICIs) in oncology, the identification of biomarkers for predicting their efficacy before starting treatment has been an unmet medical need. Many previous studies addressing this question, including a meta-analysis described herein, have led to the description of Gut OncoMicrobiome Signatures (GOMS). In this Review, we discuss how patients with cancer across various subtypes share several GOMS with individuals with seemingly unrelated chronic inflammatory disorders who, in turn, tend to have GOMS different from those of healthy individuals. We discuss findings from the aforementioned meta-analysis of GOMS patterns associated with clinical benefit from or resistance to ICIs across different cancer types (in 808 patients), with a focus on metabolic and immunological surrogate markers of intestinal dysbiosis, and propose practical guidelines to incorporate GOMS in decision-making for prospective clinical trials in immuno-oncology.

肿瘤发生与肠道失调有关，对于患有此类疾病的个体的粪便采用鸟枪式宏基因组测序可构成一种用于早期诊断几种癌症的无创性方法。抗生素的摄入和肠道微生物群组成之间的预后相关性促使研究人员开发检测肠道微生态失调的工具，以实现患者分层和以微生物群为中心的临床干预。此外，自从免疫检查点抑制剂（ICIs）在肿瘤学中出现以来，在患者治疗之前明确用于预测其疗效的生物标志物一直是一个未满足的医疗需求。许多先前针对这一问题的研究，包括本文所述的荟萃分析，都引导了对肠道肿瘤微生物组特征（GOMS）的描述。在本综述中，我们讨论了不同亚型的癌症患者如何与看似无关的慢性炎症疾病患者共享多个GOMS，而这些患者的GOMS往往与健康人不同。我们讨论了上述GOMS模式的荟萃分析结果，该荟萃分析与不同癌症类型（808例患者）ICIs的临床益处或耐药性相关，重点是肠道失调的代谢和免疫替代标记物，并提出了将GOMS纳入免疫肿瘤学前瞻性临床试验决策的实用指南。

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