间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
癌症仍是一个关键的全球健康问题,原因在于发现晚、耐药和高死亡率。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:A narrative review of the evolving role of immunotherapy in the management of esophageal and gastric cancer.
A narrative review of the evolving role of immunotherapy in the management of esophageal and gastric cancer.
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尽管免疫治疗药物已显示出临床获益并已被纳入当前的标准治疗,但双免疫联合治疗、嵌合抗原受体(CAR)T 细胞和肿瘤疫苗等新型免疫治疗方法仍需进一步研究。
尽管食管胃癌的多学科诊疗近期有所进步,整体预后仍较差,因此亟需更好的治疗选择和能够优化治疗决策的预测性生物标志物。
研究人员广泛检索PubMed数据库中2013年12月至2021年10月发表的免疫治疗相关文章,纳入英文文献;免疫治疗综述纳入Ⅰ、Ⅱ、Ⅲ期临床试验,生物标志物综述纳入前瞻性研究、回顾性研究和荟萃分析。核心内容与发现:早期免疫治疗研究主要针对复发、难治或转移性患者,显示出生存获益有限。后续研究评估了免疫治疗药物与转移性疾病一线化疗联合应用。近期数据还显示,在同步放化疗和手术后于辅助治疗阶段使用免疫治疗可改善无病生存期。微卫星高度不稳定(MSI-H)和EB病毒(EBV)阳性可预测免疫治疗应答,但不少缺乏这些标志物的患者也能获益。程序性死亡配体1(PD-L1)表达和肿瘤突变负荷(TMB)的预测价值不一,相关标志物的最佳阈值仍未明确。
免疫治疗药物已显示临床获益,并纳入当前标准治疗;但双免疫治疗联合、嵌合抗原受体(CAR)T细胞和肿瘤疫苗等新策略仍需进一步研究。随着精准医疗时代到来,还需要更完善的生物标志物来预测治疗获益。
Despite recent advances in the multidisciplinary management of esophagogastric cancer, overall prognosis remains poor. There is a need for improved treatment options, along with predictive biomarkers that improve therapeutic decision-making.
We conducted an extensive review of immunotherapy articles in the PubMed database between December 2013 and October 2021. Articles in English were included. We included phase 1, 2, and 3 clinical trials for immunotherapy review, and prospective, retrospective, and meta-analyses for biomarker review. KEY CONTENT AND FINDINGS: Initial studies of immunotherapy were performed in patients with relapsed refractory metastatic disease and demonstrated a modest survival benefit. Subsequent studies have evaluated the use of these agents in combination with first line chemotherapy for metastatic disease. Finally, recent data indicates that immunotherapy in the adjuvant setting after concurrent chemoradiation and surgery improves disease free survival. Both microsatellite instability high (MSI-H) status and Epstein-Barr virus (EBV) positivity predict response to immunotherapy, but many patients without these biomarkers still benefit. The predictive impact of programmed cell death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) have been variable, and the optimal cutoff point for these biomarkers remains poorly defined.
While immunotherapy agents have demonstrated clinical benefit and are now incorporated into the current standard of care, novel immunotherapy approaches such as dual immunotherapy combinations, chimeric antigen receptor (CAR) T cells, and tumor vaccines need to be further investigated. As the era of precision medicine beckons, refined biomarkers to predict benefit are needed.
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