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Tumor-infiltrating lymphocytes in the immunotherapy era
Cellular & Molecular Immunology ( IF 24.1 ) Pub Date : 2020-11-02 , DOI: 10.1038/s41423-020-00565-9
Sterre T Paijens 1 , Annegé Vledder 1 , Marco de Bruyn 1 , Hans W Nijman 1
Affiliation  

The clinical success of cancer immune checkpoint blockade (ICB) has refocused attention on tumor-infiltrating lymphocytes (TILs) across cancer types. The outcome of immune checkpoint inhibitor therapy in cancer patients has been linked to the quality and magnitude of T cell, NK cell, and more recently, B cell responses within the tumor microenvironment. State-of-the-art single-cell analysis of TIL gene expression profiles and clonality has revealed a remarkable degree of cellular heterogeneity and distinct patterns of immune activation and exhaustion. Many of these states are conserved across tumor types, in line with the broad responses observed clinically. Despite this homology, not all cancer types with similar TIL landscapes respond similarly to immunotherapy, highlighting the complexity of the underlying tumor-immune interactions. This observation is further confounded by the strong prognostic benefit of TILs observed for tumor types that have so far respond poorly to immunotherapy. Thus, while a holistic view of lymphocyte infiltration and dysfunction on a single-cell level is emerging, the search for response and prognostic biomarkers is just beginning. Within this review, we discuss recent advances in the understanding of TIL biology, their prognostic benefit, and their predictive value for therapy.



中文翻译:

免疫治疗时代的肿瘤浸润淋巴细胞

癌症免疫检查点阻断(ICB)的临床成功重新将注意力集中在跨癌症类型的肿瘤浸润淋巴细胞(TIL)上。癌症患者免疫检查点抑制剂治疗的结果与肿瘤微环境中 T 细胞、NK 细胞以及最近的 B 细胞反应的质量和程度有关。对 TIL 基因表达谱和克隆性进行最先进的单细胞分析揭示了显着程度的细胞异质性以及独特的免疫激活和耗竭模式。其中许多状态在肿瘤类型中是保守的,与临床观察到的广泛反应一致。尽管存在这种同源性,但并非所有具有相似 TIL 景观的癌症类型对免疫疗法的反应都相似,这凸显了潜在的肿瘤免疫相互作用的复杂性。这一观察结果进一步混淆了 TIL 对迄今为止对免疫治疗反应不佳的肿瘤类型所观察到的强大预后益处。因此,虽然单细胞水平上淋巴细胞浸润和功能障碍的整体观点正在出现,但对反应和预后生物标志物的搜索才刚刚开始。在这篇综述中,我们讨论了 TIL 生物学的最新进展、其预后益处及其对治疗的预测价值。

更新日期:2020-11-02
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