免疫检查点抑制剂增敏治疗癌症的当前趋势

IF 27.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2024-12-26 DOI:10.1186/s12943-024-02179-5

Jing Wei, Wenke Li, Pengfei Zhang, Fukun Guo, Ming Liu

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引用次数: 0

摘要

免疫检查点抑制剂（ICIs）极大地改变了各种恶性肿瘤的治疗格局，在广泛的适应症中取得了显著的临床疗效。尽管取得了这些进展，但对免疫检查点阻断剂（ICB）的耐药性仍然是一个严峻的临床挑战，其特点是反应率不稳定和疗效不持久。然而，对肿瘤复杂的内在和外在特征的研究不断深入，加深了我们对 ICI 耐药性背后机制的理解，从而有可能改善治疗效果。此外，强大的预测性生物标志物对于优化患者选择和最大限度地发挥 ICB 的疗效至关重要。最近的研究强调，多种合理的联合策略可以克服免疫检查点耐药性，提高对 ICIs 的敏感性。这些发现不仅加深了我们对肿瘤生物学的理解，还揭示了增敏剂的独特作用机制，扩大了癌症免疫疗法的临床效益。在这篇综述中，我们将探讨 ICIs 的基础生物学，讨论肿瘤免疫微环境（TIME）和临床预测生物标志物的意义，分析当前的耐药机制，并概述提高 ICIs 效力的替代性组合策略，包括使肿瘤对 ICIs 敏感的个性化策略。

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Current trends in sensitizing immune checkpoint inhibitors for cancer treatment

Immune checkpoint inhibitors (ICIs) have dramatically transformed the treatment landscape for various malignancies, achieving notable clinical outcomes across a wide range of indications. Despite these advances, resistance to immune checkpoint blockade (ICB) remains a critical clinical challenge, characterized by variable response rates and non-durable benefits. However, growing research into the complex intrinsic and extrinsic characteristics of tumors has advanced our understanding of the mechanisms behind ICI resistance, potentially improving treatment outcomes. Additionally, robust predictive biomarkers are crucial for optimizing patient selection and maximizing the efficacy of ICBs. Recent studies have emphasized that multiple rational combination strategies can overcome immune checkpoint resistance and enhance susceptibility to ICIs. These findings not only deepen our understanding of tumor biology but also reveal the unique mechanisms of action of sensitizing agents, extending clinical benefits in cancer immunotherapy. In this review, we will explore the underlying biology of ICIs, discuss the significance of the tumor immune microenvironment (TIME) and clinical predictive biomarkers, analyze the current mechanisms of resistance, and outline alternative combination strategies to enhance the effectiveness of ICIs, including personalized strategies for sensitizing tumors to ICIs.

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来源期刊

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

期刊介绍： Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.