通过靶向肿瘤相关巨噬细胞的嵌合受体工程化溶瘤病毒重振内源性抗肿瘤免疫
Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cancer immunotherapy: mechanisms, clinical applications, resistance and future directions.
Cancer immunotherapy: mechanisms, clinical applications, resistance and future directions.
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癌症免疫治疗通过利用免疫介导机制实现持久的抗肿瘤反应和长期临床获益,彻底改变了肿瘤学。与传统细胞毒性治疗不同,免疫治疗方法调节宿主-肿瘤相互作用并恢复免疫监视,从而实现可持续的肿瘤控制。本综述提供了全面的综合阐述,涵盖癌症免疫治疗的生物学基础和临床发展、癌症-免疫系统相互作用、肿瘤免疫编辑以及作为治疗干预概念框架的癌症-免疫循环。主要免疫治疗方法,包括免疫检查点抑制剂、过继细胞疗法、癌症疫苗、基于细胞因子的疗法和溶瘤病毒,已就其作用机制和临床应用进行了系统综述。特别强调监管机构批准的药物、基于适应证的临床使用、预测性生物标志物和合理的联合策略。
此外,本综述讨论了限制治疗疗效的关键挑战,包括原发性和获得性耐药、肿瘤异质性、免疫逃逸机制和免疫抑制性肿瘤微环境。还讨论了新方向,如个性化免疫治疗、基于新抗原的靶向、微生物组-免疫相互作用和人工智能支持的系统免疫学。通过整合机制见解与临床证据和耐药框架,本综述提供了关于癌症免疫治疗当前状态和未来轨迹的综合视角,为转化研究和临床实践提供了重要启示。
Cancer immunotherapy has revolutionised oncology by utilising immune-mediated mechanisms to achieve durable anti-tumour responses and long-term clinical benefits. Unlike traditional cytotoxic therapies, immunotherapeutic approaches modulate host-tumour interactions and restore immune surveillance, thereby enabling sustainable tumour control. This review provides a comprehensive synthesis covering the biological foundations and clinical development of cancer immunotherapy, cancer-immunity system interactions, tumour immunoediting, and the cancer-immunity cycle as a conceptual framework for therapeutic intervention.
Major immunotherapeutic approaches, including immune checkpoint inhibitors, adoptive cell therapies, cancer vaccines, cytokine-based therapies, and oncolytic viruses, have been systematically reviewed for their mechanisms of action and clinical applications. Particular emphasis is placed on regulatory agency-approved agents, indication-based clinical use, predictive biomarkers, and rational combination strategies.
Furthermore, this review addresses key challenges that limit therapeutic efficacy, including primary and acquired resistance, tumour heterogeneity, immune escape mechanisms, and the immunosuppressive tumour microenvironment. New directions such as personalised immunotherapy, neoantigen-based targeting, microbiome-immune interactions, and artificial intelligence-supported systems immunology are also discussed.
By integrating mechanistic insights with clinical evidence and resistance frameworks, this review provides a consolidated perspective on the current state and future trajectory of cancer immunotherapy, offering important implications for translational research and clinical practice.
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