金属和类金属对PD-1/PD-L1轴及肿瘤免疫的调控：机制见解与人类健康意义
Modulation of the PD-1/PD-L1 axis and tumor immunity by metals and metalloids: mechanistic insights and human health implications.
摘要(中文译文)
免疫检查点维持免疫稳态，但其失调可损害抗肿瘤免疫并促进肿瘤免疫逃逸。越来越多的证据表明，金属和类金属是免疫检查点信号的重要调节因子；然而，其潜在机制及对人类健康的更广泛影响尚未被系统整合。在本综述中，我们全面检索了截至2026年3月的PubMed、Web of Science和Scopus数据库，以识别在人类、动物和实验模型中考察金属和类金属相关免疫检查点表达或功能变化的研究。现有证据提示，金属和类金属以高度依赖背景的方式调节免疫检查点，其中对PD-1/PD-L1轴影响的证据最强，而其他检查点的证据仍然有限。在机制上，这些效应汇聚于肿瘤免疫微环境重塑、氧化应激、缺氧信号传导、炎症信号转导以及抑癌基因和蛋白质稳态通路，从而影响T细胞耗竭、肿瘤免疫逃逸以及对免疫检查点抑制剂（ICIs）的应答。新兴的临床证据进一步提示，微量元素状态，特别是锌和铜相关指标，可能作为免疫肿瘤学中的候选生物标志物具有价值。然而，大多数证据仍处于临床前阶段，将金属和类金属相关检查点失调与全身不良健康结局或临床可操作干预措施联系起来的直接人类证据仍然有限。总体而言，本综述将暴露生物学与肿瘤免疫学联系起来，并确定金属和类金属相关的免疫检查点调节是肿瘤免疫改变的合理促成因素，也是未来转化研究和人群研究的优先方向。
Abstract
Immune checkpoints maintain immune homeostasis, but their dysregulation can impair antitumor immunity and promote tumor immune evasion. Accumulating evidence indicates that metals and metalloids are important modulators of immune checkpoint signaling; however, their underlying mechanisms and broader implications for human health have not been systematically synthesized. In this review, we conducted a comprehensive search of PubMed, Web of Science, and Scopus through March 2026 to identify peer-reviewed studies examining metal- and metalloid-associated changes in immune checkpoint expression or function in human, animal, and experimental models. Current evidence suggests that metals and metalloids modulate immune checkpoints in a highly context-dependent manner, with the strongest support for effects on the PD-1/PD-L1 axis, whereas evidence for other checkpoints remains limited. Mechanistically, these effects converge on remodeling of the tumor immune microenvironment, oxidative stress, hypoxia signaling, inflammatory signal transduction, and tumor suppressor and protein homeostasis pathways, thereby influencing T-cell exhaustion, tumor immune evasion, and responses to immune checkpoint inhibitors (ICIs). Emerging clinical evidence further suggests that trace-element status, particularly zinc- and copper-related measures, may have value as candidate biomarkers in immuno-oncology. However, most evidence remains preclinical, and direct human evidence linking metal- and metalloid-associated checkpoint dysregulation to systemic adverse health outcomes or clinically actionable interventions is still limited. Overall, this review connects exposure biology with cancer immunology and identifies metal- and metalloid-associated immune checkpoint modulation as a plausible contributor to altered tumor immunity and a priority for future translational and population-based research.
如何引用
AMA
Zhenyu Lu, Guangcan Chen, Jingle Qiu, Xia Huo, Xijin Xu. Modulation of the PD-1/PD-L1 axis and tumor immunity by metals and metalloids: mechanistic insights and human health implications.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1862118.
APA
Zhenyu Lu, Guangcan Chen, Jingle Qiu, Xia Huo, Xijin Xu (2026). Modulation of the PD-1/PD-L1 axis and tumor immunity by metals and metalloids: mechanistic insights and human health implications.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1862118
GB/T 7714
Zhenyu Lu, Guangcan Chen, Jingle Qiu, Xia Huo, Xijin Xu. Modulation of the PD-1/PD-L1 axis and tumor immunity by metals and metalloids: mechanistic insights and human health implications.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1862118.
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