间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
癌症仍是一个关键的全球健康问题,原因在于发现晚、耐药和高死亡率。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Roles and functions of tumor-infiltrating lymphocytes and tertiary lymphoid structures in gastric cancer progression.
Roles and functions of tumor-infiltrating lymphocytes and tertiary lymphoid structures in gastric cancer progression.
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胃癌(GC)是癌症死亡的主要原因之一,具有显著的分子异质性和免疫抑制性肿瘤微环境(TME)特征,限制了治疗效果。本综述阐明了三级淋巴结构(TLS)和TIL(肿瘤浸润淋巴细胞)(TILs)在GC进展中的双重作用。TLS是在慢性炎症下形成的异位淋巴器官,通过促进效应T/B细胞相互作用和抗原呈递,与改善的生存率和免疫治疗敏感性相关。相反,免疫抑制性TME组分如调节性T细胞(Tregs)和肿瘤相关巨噬细胞(TAMs)通过细胞因子介导的抑制和检查点激活(PD-1/PD-L1)驱动免疫逃逸。CD8+ T细胞发挥情境依赖性效应,高浸润降低复发风险,但在PD-L1丰富的微环境中矛盾性地诱导耗竭。Th17和记忆T细胞通过IL-17驱动的血管生成和CD45RO+免疫记忆动态进一步调节疾病。基于多组学的TLS评分和联合治疗成为克服耐药的有前景策略。
Gastric cancer (GC), a leading cause of cancer mortality, exhibits profound molecular heterogeneity and immunosuppressive tumor microenvironment (TME) features that limit therapeutic efficacy. This review elucidates the dual roles of tertiary lymphoid structures (TLS) and tumor-infiltrating lymphocytes (TILs) in GC progression. TLS, ectopic lymphoid organs formed under chronic inflammation, correlate with improved survival and immunotherapy sensitivity by fostering effector T/B cell interactions and antigen presentation.
Conversely, immunosuppressive TME components like regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) drive immune evasion via cytokine-mediated suppression and checkpoint activation (PD-1/PD-L1). CD8 + T cells exert context-dependent effects, with high infiltration reducing recurrence risk but paradoxically inducing exhaustion in PD-L1-rich microenvironments.
Th17 and memory T cells further modulate disease through IL-17-driven angiogenesis and CD45RO + immune memory dynamics. Multi-omics-based TLS scoring and combinatorial therapies emerge as promising strategies to overcome resistance.
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