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综述文章:益生菌介导增强HER2阳性乳腺癌的检查点抑制剂阻断作用

Review Article: Probiotics-Mediated Enhancement of Checkpoint Inhibitor Blockade for HER2+ Breast Cancer.

作者信息

Ho Mai, Bonavida Benjamin

机构信息

Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, California 90095.

Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Johnson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90025-1747, USA.

出版信息

Crit Rev Oncog. 2025;30(2):37-47. doi: 10.1615/CritRevOncog.2025058633.


DOI:10.1615/CritRevOncog.2025058633
PMID:40561431
Abstract

Immune checkpoint inhibitors (ICIs) have significantly improved survival rates for many types of cancer, giving patients survival prognoses that had been previously unattainable. Unfortunately, in many advanced cancers, including breast cancer (BC), objective response rates (ORRs) have been reported to be between 5% and 25% and immune-related adverse events (irAEs) can be severe, emphasizing the need to improve the effectiveness of ICIs while minimizing irAEs. In recent years, probiotics and various bacteria consortia have gained growing recognition for their application in immunotherapies for various cancers. Many preclinical models have demonstrated that probiotics significantly influence the gut microbiome, enhancing the production of beneficial metabolites and promoting interactions with cytotoxic T cells to amplify the antitumor effects of ICIs. For the treatment of HER2+ BC, current clinical trials have administered ICIs in combination with anti-HER2 agents (e.g., trastuzumab) to enhance treatment efficacy. Thus far, this combination has shown promising results, especially in patients with advanced PDL1-positive disease. However, as these trials are still ongoing, the efficacy of immune checkpoint blockade (ICB) therapy for HER2+ BCs remains inconclusive and requires further investigation. Thus, this review discusses the use of probiotics in ICB therapy, focusing on the potential role of probiotics in HER2+ BC response to ICIs, their underlying mechanisms and challenges.

摘要

免疫检查点抑制剂(ICIs)显著提高了多种癌症的生存率,使患者获得了以前无法实现的生存预后。不幸的是,在包括乳腺癌(BC)在内的许多晚期癌症中,据报道客观缓解率(ORRs)在5%至25%之间,且免疫相关不良事件(irAEs)可能很严重,这凸显了提高ICIs有效性同时将irAEs降至最低的必要性。近年来,益生菌和各种细菌联合体在各种癌症免疫治疗中的应用越来越受到认可。许多临床前模型表明,益生菌显著影响肠道微生物群,增强有益代谢物的产生,并促进与细胞毒性T细胞的相互作用,以放大ICIs的抗肿瘤作用。对于HER2+ BC的治疗,目前的临床试验已将ICIs与抗HER2药物(如曲妥珠单抗)联合使用,以提高治疗效果。到目前为止,这种联合疗法已显示出有希望的结果,尤其是在晚期PDL1阳性疾病患者中。然而,由于这些试验仍在进行中,免疫检查点阻断(ICB)疗法对HER2+ BC的疗效仍不确定,需要进一步研究。因此,本综述讨论了益生菌在ICB疗法中的应用,重点关注益生菌在HER2+ BC对ICIs反应中的潜在作用、其潜在机制和挑战。

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