CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Beyond the tumor microenvironment: Orchestrating systemic T‑cell response for next‑generation cancer immunotherapy (Review).
Beyond the tumor microenvironment: Orchestrating systemic T‑cell response for next‑generation cancer immunotherapy (Review).
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免疫检查点阻断疗法已经彻底改变了癌症治疗格局,然而其临床疗效仍局限于具有特定肿瘤类型的部分患者。本综述从局部和全身两个视角对T细胞介导的抗肿瘤免疫进行了全面分析,特别强调CD8+ T细胞作为主要效应细胞的作用。本综述讨论了肿瘤微环境(TME)、周围淋巴组织和外周循环之间复杂的转运过程如何为肿瘤逃避免疫监视创造多种机会。在TME内,综述了T细胞排斥机制、抗原特异性以及T细胞耗竭状态谱系——从祖细胞耗竭T细胞到终末耗竭T细胞表型。在局部TME之外,分析了肿瘤引流淋巴结和三级淋巴结构在维持可持续抗肿瘤免疫中的关键作用,以及循环T细胞作为生物标志物和治疗靶点的重要意义。这一全身视角为理解抗肿瘤免疫的动态本质提供了见解,并提出了下一代免疫治疗的潜在策略,包括靶向多个免疫区室的联合方案以实现最佳治疗结局。
Immune checkpoint blockade therapy has revolutionized cancer treatment, yet its clinical efficacy remains limited to a subset of patients with specific tumor types. The present review provides a comprehensive analysis of T cell‑mediated antitumor immunity from both local and systemic perspectives, with particular emphasis on CD8 + T cells as primary effectors. The review discusses how the complex trafficking between the tumor microenvironment (TME), surrounding lymphoid tissues and peripheral circulation creates multiple opportunities for tumors to evade immune surveillance.
Within the TME, T‑cell exclusion mechanisms, antigen specificity and the spectrum of T‑cell exhaustion states, from progenitor exhausted T cells to terminally exhausted T‑cell phenotypes, are reviewed. Beyond the local TME, the crucial roles of tumor‑draining lymph nodes and tertiary lymphoid structures in maintaining sustainable antitumor immunity, as well as the significance of circulating T cells as both biomarkers and therapeutic targets, are analyzed.
This systemic perspective provides insights into the dynamic nature of antitumor immunity and suggests potential strategies for next‑generation immunotherapies, including combination approaches targeting multiple immune compartments to achieve optimal therapeutic outcomes.
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