免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Autophagy meets tissue-resident memory: Emerging crosstalk and therapeutic opportunities in cutaneous melanoma.
Autophagy meets tissue-resident memory: Emerging crosstalk and therapeutic opportunities in cutaneous melanoma.
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黑色素瘤是一种高度免疫原性的人类癌症,其特征是肿瘤微环境(TME)内存在复杂的免疫反应。其中,TIL(肿瘤浸润淋巴细胞)(TILs)和组织驻留记忆T细胞(TRM)与良好预后和对免疫检查点阻断的应答强烈相关,反映了它们在维持抗肿瘤免疫中的核心作用。新出现的证据表明,这些T细胞亚群的活性和持续性受到自噬的关键影响,自噬是一种细胞过程,在TME典型的营养受限和应激条件下维持代谢适应性、防止耗竭并支持效应功能。理解自噬-T细胞轴可能为旨在增强黑色素瘤免疫监视和改善患者预后的治疗策略开辟新途径。在这篇综述中,我们探讨了皮肤黑色素瘤中TRM细胞生物学与自噬之间的交叉,概述了TRM在肿瘤环境中的分化和功能,回顾了黑色素瘤细胞内的自噬,并审查了它们之间潜在串扰的证据。
我们进一步讨论了自噬如何塑造TRM的发育、维持和功能,同时肿瘤内在的自噬调节TIL和TRM介导的应答,并在结论中强调了治疗机会,包括那些正在注册临床试验中研究的机会。通过提供对这种复杂相互作用的见解,本综述旨在激发进一步研究,并支持针对黑色素瘤的靶向TRM治疗策略的开发。
Melanoma is a highly immunogenic human cancer characterized by complex immune responses within the tumor microenvironment (TME). Among these, tumor-infiltrating lymphocytes (TILs) and tissue-resident memory T cells (TRM) are strongly associated with favorable prognosis and response to immune checkpoint blockade, reflecting their central role in sustaining anti-tumor immunity. Emerging evidence suggests that the activity and persistence of these T cell subsets are critically influenced by autophagy, a cellular process that maintains metabolic fitness, prevents exhaustion, and supports effector functions under nutrient-limited and stressful conditions typical of the TME.
Understanding the autophagy-T cell axis may open new avenues for therapeutic strategies aimed at enhancing melanoma immunosurveillance and improving patient outcomes. In this review, we explore the intersection between TRM-cell biology and autophagy in cutaneous melanoma, outlining TRM differentiation and functions in the tumor setting, reviewing autophagy within melanoma cells, and examining evidence for their potential crosstalk.
We further discuss how autophagy may shape TRM development, maintenance, and function, while tumor-intrinsic autophagy modulates TIL and TRM-mediated responses, and conclude by highlighting therapeutic opportunities, including those under investigation in registered clinical trials. By providing insights into this intricate interplay, the review aims to stimulate further investigation and support the development of targeted TRM-based therapeutic strategies for melanoma.
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