免疫疗法
医学
癌症
免疫检查点
封锁
癌症免疫疗法
T细胞
癌症研究
免疫系统
免疫学
肺癌
MHC I级
主要组织相容性复合体
肿瘤科
内科学
受体
作者
Jon Zugazagoitia,Handerson Rafael Osma,Javier Baena,Álvaro C. Ucero,Luis Paz‐Ares
标识
DOI:10.1158/1078-0432.ccr-23-1159
摘要
Abstract Platinum-based chemotherapy plus PD-1 axis blockade is the standard of care in the front-line treatment of extensive-stage small cell lung cancer (ES-SCLC). Despite the robust and consistent increase of long-term survival with PD-1 axis inhibition, the magnitude of the benefit from immunotherapy appears lower as compared to other solid tumors. Several immune evasive mechanisms have been shown to be prominently altered in human SCLC, including, among others, T cell exclusion, downregulation of components of the MHC-class I antigen processing and presentation machinery, or upregulation of macrophage inhibitory checkpoints. New immunotherapies aiming to target some of these dominant immune suppressive features are being intensively evaluated preclinically and clinically in SCLC. They include strategies to enhance the efficacy and/or reverse features that promote intrinsic resistance to PD-1 axis inhibition (e.g., restoring MHC-class I deficiency, targeting DNA damage response [DDR]), and novel immunomodulatory agents beyond T cell checkpoint blockers (e.g., T cell redirecting strategies, antibody drug conjugates [ADCs], or macrophage checkpoint blockers). Among them, DLL3-targeted bi-specific T-cell engagers (BiTEs) are the ones that have shown the most compelling preliminary evidence of clinical efficacy, and hold promise as therapies that might contribute to further improve patient outcomes in this disease. Here, we first provide a brief overview of key tumor microenvironment features of human SCLC. Then, we update the current clinical evidence with immune checkpoint blockade and review other emerging immunotherapy strategies that are gaining increasing attention in SCLC. We finally summarize our future perspective on immunotherapy and precision oncology for this disease.
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