Disis Mary L, Bernhard Helga, Jaffee Elizabeth M
Center for Translational Medicine in Women's Health, Tumor Vaccine Group, University of Washington, Seattle, WA, USA.
Lancet. 2009 Feb 21;373(9664):673-83. doi: 10.1016/S0140-6736(09)60404-9.
The stimulation of a tumour-specific T-cell response has several theoretical advantages over other forms of cancer treatment. First, T cells can home in to antigen-expressing tumour deposits no matter where they are located in the body-even in deep tissue beds. Additionally, T cells can continue to proliferate in response to immunogenic proteins expressed in cancer until all the tumour cells are eradicated. Finally, immunological memory can be generated, allowing for eradication of antigen-bearing tumours if they reoccur. We will highlight two direct methods of stimulating tumour-specific T-cell immunity: active immunisation with cancer vaccines and infusion of competent T cells via adoptive T-cell treatment. Preclinical and clinical studies have shown that modulation of the tumour microenvironment to support the immune response is as important as stimulation of the most appropriate effector T cells. The future of T-cell immunity stimulation to treat cancer will need combination approaches focused on both the tumour and the T cell.
与其他形式的癌症治疗相比,刺激肿瘤特异性T细胞反应具有几个理论优势。首先,T细胞能够归巢至表达抗原的肿瘤沉积物,无论它们位于身体的何处——即使是在深部组织床中。此外,T细胞能够响应癌症中表达的免疫原性蛋白持续增殖,直到所有肿瘤细胞被根除。最后,可以产生免疫记忆,使得如果携带抗原的肿瘤复发能够将其根除。我们将重点介绍两种刺激肿瘤特异性T细胞免疫的直接方法:通过癌症疫苗进行主动免疫和通过过继性T细胞治疗输注有功能的T细胞。临床前和临床研究表明,调节肿瘤微环境以支持免疫反应与刺激最合适的效应T细胞同样重要。刺激T细胞免疫来治疗癌症的未来将需要专注于肿瘤和T细胞的联合方法。