CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immune checkpoint inhibitors and cellular immunotherapy for advanced gastric, gastroesophageal cancer: a long pathway.
Immune checkpoint inhibitors and cellular immunotherapy for advanced gastric, gastroesophageal cancer: a long pathway.
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尽管胃/胃食管结合部癌(G/GEJC)发病率和死亡率全球下降,东亚仍面临较大疾病负担。晚期患者在多线化疗后治疗选择有限,中位OS不足1年。包括免疫检查点抑制剂(ICI)和细胞免疫疗法在内的免疫治疗,通过逆转肿瘤微环境免疫抑制改变癌症治疗前景。本综述梳理针对PD-1/PD-L1和CTLA-4/B7免疫抑制信号轴的ICI临床应用。ICI最初获批用于既往多线治疗的晚期胃癌和胃食管结合部癌二线治疗;目前对经生物标志物筛选的患者,ICI与化疗和靶向治疗联合已成为主流方案。大量证据提示微卫星不稳定性(MSI)、PD-L1表达、肿瘤突变负荷(TMB)和EBV状态可能帮助识别适宜患者。本文还讨论晚期G/GEJC中ICI局限和前景,以及新型CAR-T 疗法的首次临床应用。
Although the incidence rate and mortality of gastric/gastroesophageal cancer (G/GEJC) are declining globally, G/GEJC remains a health issue in East Asia. When diagnosed as advanced stage, treatment after serial lines of chemotherapy is limited, with a median overall survival of less than 1 year. Immunotherapy, including immune checkpoint inhibitors (ICIs) and cellular immunotherapy, has changed the prospects of cancer therapy by reversing immune suppression in the tumor microenvironment. As part of this review, we enumerated the clinical uses of ICIs related to the immunosuppressive signaling axis PD-1/PD-L1 and CTLA-4/B7.
ICIs were initially approved as a secondary treatment option for patients with severe pretreating advanced gastric and gastroesophageal cancer (AG/GEJC). Till now, it has become the mainstream therapy in combination with chemotherapy and targeted therapy for patients identified by biomarkers. Numerous evidence showed microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden (TMB) and Epstein-Barr virus (EBV) status might be indicative to the use of ICIs.
In addition, we discussed the current limitations and prospects of ICIs in AG/GGEJC, as well as the first clinical application of novel CAR-T cell therapies.
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