免疫检查点阻断剂促进T细胞应答的影响因素

Influence factors of immune-checkpoint blockade on T cell response

抑制免疫调节检查点,比如PD-1/PD-L1与CTLA-4,是癌症免疫治疗的前沿科学。然而这样的免疫疗法只对少部分患者的癌症形成有效。本文通过分析肿瘤的成瘤原因、微环境及其自体相关因素后发现这些因素均会导致免疫检查点阻断剂在体内失去T细胞免疫应答。因此,本文描述了免疫系统与宿主肠道微生物群可调控癌症免疫治疗的应答,并且在使用免疫检查点阻断剂的同时或之前调节肠道微生物群可以优化治疗效果。

Inhibition of immune regulatory checkpoints, such as CTLA-4 and the PD- 1-PD-L1 axis, is at the forefront of immunotherapy for cancers of various types. However, such immunotherapies fail to control neoplasia in a significant proportion of patients. Here, we review how a range of cancer-cell-autonomous cues, tumor-microenvironmental factors, and host factors might account for the heterogeneous responses and failures encountered during therapies using immune-checkpoint blockade. Furthermore, we describe the emerging evidence that interrelationship between the immune system and the host microbiota can determine responses to cancer therapies, and we propose that modulation of gut microbiome could optimize therapeutic outcomes of immune- checkpoint blockade.