封锁
免疫检查点
免疫疗法
肺癌
免疫系统
医学
免疫抑制
癌症
T细胞
癌症研究
免疫学
肿瘤科
内科学
受体
作者
Jessica Konen,Haoyi Wu,Don L. Gibbons
标识
DOI:10.1016/j.tips.2024.04.006
摘要
Immune checkpoint blockade (ICB) therapy works by inhibiting suppressive checkpoints that become upregulated after T cell activation, like PD-1/PD-L1 and CTLA-4. While the initial FDA approvals of ICB have revolutionized cancer therapies and fueled a burgeoning immuno-oncology field, more recent clinical development of new agents has been slow. Here, focusing on lung cancer, we review the latest research uncovering tumor cell intrinsic and extrinsic ICB resistance mechanisms as major hurdles to treatment efficacy and clinical progress. These include genomic and non-genomic tumor cell alterations, along with host and microenvironmental factors like the microbiome, metabolite accumulation, and hypoxia. Together, these factors can cooperate to promote immunosuppression and ICB resistance. Opportunities to prevent resistance are constantly evolving in this rapidly expanding field, with the goal of moving toward personalized immunotherapeutic regimens.
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