Thomas Anish, Jakopovic Marko
National Cancer Institute, National Institutes of Health, Center for Cancer Research, Thoracic and GI Oncology Branch , Building 10-CRC/4-5330, Bethesda, MD 20892 , USA.
Expert Opin Biol Ther. 2014 Aug;14(8):1061-4. doi: 10.1517/14712598.2014.925874. Epub 2014 May 30.
Activation of the host immune system represents an attractive treatment approach for cancers. In non-small-cell lung cancer (NSCLC), a variety of immunotherapies, including nonspecific immune stimulants, vaccines and checkpoint inhibitors, have been evaluated in clinical trials. Several randomized Phase III trials have failed to demonstrate clinical benefit from nonspecific immune stimulants and vaccines in the overall trial populations. Activity of vaccines in subsets of patients in these trials needs further evaluation. Unlike vaccines aimed at stimulating a cellular immune response to antigens differentially expressed in cancers, checkpoint inhibitors aim at overcoming immune inhibitory signals in the tumor microenvironment via pharmacological inhibition of immune checkpoints - a crucial tumoral immune escape mechanism. Early clinical trials of checkpoint inhibitors showed promising results with some durable responses. Better understanding of the mechanisms of immunosuppression specific to NSCLC will be crucial for successful patient selection for immunotherapy.
激活宿主免疫系统是一种颇具吸引力的癌症治疗方法。在非小细胞肺癌（NSCLC）中，包括非特异性免疫刺激剂、疫苗和检查点抑制剂在内的多种免疫疗法已在临床试验中进行了评估。几项随机III期试验未能在整体试验人群中证明非特异性免疫刺激剂和疫苗具有临床益处。这些试验中疫苗在部分患者亚组中的活性需要进一步评估。与旨在刺激对癌症中差异表达抗原的细胞免疫反应的疫苗不同，检查点抑制剂旨在通过对免疫检查点的药理抑制来克服肿瘤微环境中的免疫抑制信号——这是一种关键的肿瘤免疫逃逸机制。检查点抑制剂的早期临床试验显示出了一些持久反应的喜人结果。更好地理解NSCLC特有的免疫抑制机制对于成功选择免疫治疗患者至关重要。
