Leen Ann M, Rooney Cliona M, Foster Aaron E
Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, Texas 77030, USA.
Annu Rev Immunol. 2007;25:243-65. doi: 10.1146/annurev.immunol.25.022106.141527.
Adoptive transfer of antigen-specific T lymphocytes is a powerful therapy for the treatment of opportunistic disease and some virus-associated malignancies such as Epstein-Barr virus-positive post-transplant lymphoproliferative disease. However, this strategy has been less successful in patients with nonviral cancers owing to their many and varied immune evasion mechanisms. These mechanisms include downregulation of target antigens and antigen-presenting machinery, secretion of inhibitory cytokines, and recruitment of regulatory immune cells to the tumor site. With increased understanding of the tumor microenvironment and the behavior and persistence of ex vivo-manipulated, adoptively transferred T cells, two novel approaches for increasing the efficacy of T cell therapy have been proposed. The first involves genetic modification of tumor-specific T cells to improve their biological function, for example by augmenting their ability to recognize tumor cells or their resistance to tumor-mediated immunosuppression. The second requires modifications to the host environment to improve the homeostatic expansion of infused T cells or to eliminate inhibitory T cell subsets. In this review, we discuss current, promising strategies to improve adoptive T cell therapy for the treatment of cancer.
抗原特异性T淋巴细胞的过继转移是治疗机会性疾病和某些病毒相关恶性肿瘤（如爱泼斯坦-巴尔病毒阳性移植后淋巴增殖性疾病）的一种有效疗法。然而，由于非病毒性癌症患者存在多种免疫逃避机制，这种策略在他们身上的成功率较低。这些机制包括靶抗原和抗原呈递机制的下调、抑制性细胞因子的分泌以及调节性免疫细胞向肿瘤部位的募集。随着对肿瘤微环境以及体外操作的过继转移T细胞的行为和持久性的了解不断增加，人们提出了两种提高T细胞治疗疗效的新方法。第一种方法涉及对肿瘤特异性T细胞进行基因改造，以改善其生物学功能，例如增强其识别肿瘤细胞的能力或提高其对肿瘤介导的免疫抑制的抵抗力。第二种方法需要对宿主环境进行改造，以改善注入的T细胞的稳态扩增或消除抑制性T细胞亚群。在这篇综述中，我们讨论了当前有前景的策略，以改善过继性T细胞疗法在癌症治疗中的应用。
