靶向巨噬细胞的癌症治疗策略
Macrophage-directed therapeutic strategies in cancer.
肿瘤相关巨噬细胞(TAMs)是肿瘤微环境的主要组成部分,具有显著的功能可塑性,根据所处的微环境信号,既可表现为促进肿瘤进展的免疫抑制细胞,也可表现为支持抗肿瘤免疫的免疫刺激细胞。
英文原题:After a Decade of Therapy Revolution in Cutaneous Melanoma-Perspectives on Emerging Treatment Strategies.
在过去十年中,得益于免疫肿瘤学和精准医学的进步,皮肤黑色素瘤的治疗范式发生了深刻变革。
在过去十年中,免疫肿瘤学和精准医学的进步强烈地改变了皮肤黑色素瘤的治疗范式。在免疫检查点阻断和靶向治疗成功的基础上,新的治疗策略现在旨在提高疗效、克服耐药性并延长缓解的持久性。本文介绍了支持其临床使用的新辅助治疗临床试验。此外,总结了联合免疫检查点抑制的最新进展,如双抗LAG-3或抗TIGIT联合抗PD-1阻断、下一代双特异性抗体开发、基于mRNA的疫苗在临床实践中的应用以及病灶内治疗。此外,还概述了新型细胞方法日益增长的重要性,如使用TIL(肿瘤浸润淋巴细胞)或工程化T细胞的过继细胞疗法。通过整合近期临床和转化研究的见解,本综述强调了有前景的治疗途径,并随着治疗顺序和生物标志物研究,概述了未来黑色素瘤管理的关键挑战。本综述旨在总结选定的正在进行中的临床研究,并概述全身性黑色素瘤治疗的前瞻性方向。
Over the past decade, the therapeutic paradigm of cutaneous melanoma has been transformed strongly, driven by advances in immuno-oncology and precision medicine. Building on the success of immune checkpoint blockade and targeted therapy, new treatment strategies now aim to improve efficacy, overcome resistance, and prolong the durability of responses. Clinical trials on neoadjuvant therapy supporting its clinical use are presented. Furthermore, the latest progress in combinatorial immune checkpoint inhibition such as dual anti-LAG-3 or anti-TIGIT with anti-PD-1 blockade, next-generation bispecific antibody development, mRNA-based vaccines in clinical practice, and intralesional therapies are summarized. Additionally, it outlines the growing significance of novel cellular approaches, such as adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) or engineered T cells. By integrating insights from recent clinical and translational research, the review highlights promising therapeutic avenues and with treatment sequencing and biomarker research, it outlines key challenges for future melanoma management. This review aims to summarize selected ongoing clinical studies and outline prospective directions in systemic melanoma therapy.
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