Clinical Tumor Biology and Immunotherapy Unit, Ludwig Center for Cancer Research of the University of Lausanne, and Service of Radiation Oncology, Lausanne University Hospital Center, CH-1011 Lausanne, Switzerland.
Trends Immunol. 2012 Jul;33(7):364-72. doi: 10.1016/j.it.2012.02.006. Epub 2012 Mar 23.
Memory and effector T cells have the potential to counteract cancer progression, but often fail to control the disease, essentially because of three main stumbling blocks. First, clonal deletion leads to relatively low numbers or low-to-intermediate T cell receptor (TCR) affinity of self/tumor-specific T cells. Second, the poor innate immune stimulation by solid tumors is responsible for inefficient priming and boosting. Third, T cells are suppressed in the tumor microenvironment by inhibitory signals from other immune cells, stroma and tumor cells, which induces T cell exhaustion, as demonstrated in metastases of melanoma patients. State-of-the-art adoptive cell transfer and active immunotherapy can partially overcome the three stumbling blocks. The reversibility of T cell exhaustion and novel molecular insights provide the basis for further improvements of clinical immunotherapy.
记忆 T 细胞和效应 T 细胞具有抵抗癌症进展的潜力，但常常无法控制疾病，主要有三个原因。首先，克隆性缺失导致自身/肿瘤特异性 T 细胞数量相对较少或 T 细胞受体 (TCR) 亲和力较低至中等。其次，实体瘤先天免疫刺激作用差，导致初始和增强效率低下。第三，肿瘤微环境中的抑制性信号会抑制 T 细胞，这种抑制作用来自其他免疫细胞、基质和肿瘤细胞，导致 T 细胞耗竭，在黑色素瘤患者的转移灶中得到了证实。目前的过继细胞转移和主动免疫疗法可以部分克服这三个障碍。T 细胞耗竭的可逆性和新的分子见解为进一步改善临床免疫疗法提供了基础。
