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靶向调节肠道和肿瘤内微生物群以改善免疫检查点抑制剂反应的质量。

Targeted modulation of gut and intra-tumor microbiota to improve the quality of immune checkpoint inhibitor responses.

机构信息

Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.

Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China; Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.

出版信息

Microbiol Res. 2024 May;282:127668. doi: 10.1016/j.micres.2024.127668. Epub 2024 Feb 29.

Abstract

Immune checkpoint inhibitor (ICI) therapies, such as those blocking the interaction of PD-1 with its ligands, can restore the immune-killing function of T cells. However, ICI therapy is clinically beneficial in only a small number of patients, and it is difficult to predict post-treatment outcomes, thereby limiting its widespread clinical use. Research suggests that gut microbiota can regulate the host immune system and affect cancer progression and treatment. Moreover, the effectiveness of immunotherapy is related to the composition of the patient's gut microbiota; different gut microbial strains can either activate or inhibit the immune response. However, the importance of the microbial composition within the tumor has not been explored until recently. This study describes recent advances in the crosstalk between microbes in tumors and gut microbiota, which can modulate the tumor microbiome by directly translocating into the tumor and altering the tumor microenvironment. This study focused on the potential manipulation of the tumor and gut microbiota using fecal microbiota transplantation (FMT), probiotics, antimicrobials, prebiotics, and postbiotics to enrich immune-boosting bacteria while decreasing unfavorable bacteria to proactively improve the efficacy of ICI treatments. In addition, the use of genetic technologies and nanomaterials to modify microorganisms can largely optimize tumor immunotherapy and advance personalized and precise cancer treatment.

摘要

免疫检查点抑制剂(ICI)疗法,如阻断 PD-1 与其配体相互作用的疗法,可以恢复 T 细胞的免疫杀伤功能。然而,ICI 疗法在临床上仅对少数患者有益,且难以预测治疗后的结果,从而限制了其广泛的临床应用。研究表明,肠道微生物群可以调节宿主免疫系统,影响癌症的进展和治疗。此外,免疫疗法的效果与患者肠道微生物群的组成有关;不同的肠道微生物菌株可以激活或抑制免疫反应。然而,直到最近,肿瘤内微生物组成的重要性才被探索。本研究描述了肿瘤内微生物与肠道微生物群之间相互作用的最新进展,这些相互作用可以通过直接转移到肿瘤中并改变肿瘤微环境来调节肿瘤微生物组。本研究重点关注使用粪便微生物移植(FMT)、益生菌、抗菌药物、益生元和后生元来操纵肿瘤和肠道微生物群的潜力,以富集增强免疫的细菌,同时减少不利细菌,从而主动提高 ICI 治疗的效果。此外,利用遗传技术和纳米材料修饰微生物可以在很大程度上优化肿瘤免疫治疗,并推进个性化和精准的癌症治疗。

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