TCF-1 CD8 T 细胞群已成为长期免疫记忆的关键决定因素。这种细胞群具有类似干细胞的特性，通过驱动受感染细胞的持续杀伤和维持免疫-癌症平衡来改善疾病结果。在免疫反应过程中，多种因素（包括抗原沉积和亲和力、炎症环境和 T 细胞启动动力学）聚集在一起，导致 CD8 T 细胞分化发生偏差。尽管这些机制在急性和慢性疾病环境中会发生变化，但在每种情况下都会形成表型相似的干细胞样 TCF-1 CD8 T 细胞状态。在这里，我们描述了淋巴结和肿瘤微环境内的特殊微环境，这些微环境促进干细胞样 TCF-1 CD8 T 细胞群的生成或重新激活。我们强调了靶向干细胞样 CD8 T 细胞生态位以增强疫苗接种和癌症免疫治疗以及追踪干细胞样 CD8 T 细胞作为治疗功效生物标志物的轨迹的潜力。版权所有 © 2024 Elsevier Ltd。保留所有权利。

TCF-1+ CD8+ T cell populations have emerged as critical determinants for long-lived immunological memory. This cell population has stem-like properties and is implicated in improved disease outcomes by driving sustained killing of infected cells and maintaining the immune-cancer equilibrium. During an immune response, several factors, including antigen deposition and affinity, the inflammatory milieu, and T cell priming dynamics, aggregate to skew CD8+ T cell differentiation. Although these mechanisms are altered between acute and chronic disease settings, phenotypically similar stem-like TCF-1+ CD8+ T cell states are formed in each of these settings. Here, we characterize the specialized microenvironments within lymph nodes and the tumor microenvironment, which foster the generation or re-activation of stem-like TCF-1+ CD8+ T cell populations. We highlight the potential for targeting the stem-like CD8+ T cell niche to enhance vaccination and cancer immunotherapy and to track the trajectory of stem-like CD8+ T cells as biomarkers of therapeutic efficacy.Copyright © 2024 Elsevier Ltd. All rights reserved.