McKee Mark D, Roszkowski Jeffrey J, Nishimura Michael I
Department of Surgery, The University of Chicago, Chicago, IL, USA.
J Transl Med. 2005 Sep 20;3:35. doi: 10.1186/1479-5876-3-35.
In the last two decades, great advances have been made studying the immune response to human tumors. The identification of protein antigens from cancer cells and better techniques for eliciting antigen specific T cell responses in vitro and in vivo have led to improved understanding of tumor recognition by T cells. Yet, much remains to be learned about the intricate details of T cell-tumor cell interactions. Though the strength of interaction between T cell and target is thought to be a key factor influencing the T cell response, investigations of T cell avidity, T cell receptor (TCR) affinity for peptide-MHC complex, and the recognition of peptide on antigen presenting targets or tumor cells reveal complex relationships. Coincident with these investigations, therapeutic strategies have been developed to enhance tumor recognition using antigens with altered peptide structures and T cells modified by the introduction of new antigen binding receptor molecules. The profound effects of these strategies on T cell-tumor interactions and the clinical implications of these effects are of interest to both scientists and clinicians. In recent years, the focus of much of our work has been the avidity and effector characteristics of tumor reactive T cells. Here we review concepts and current results in the field, and the implications of therapeutic strategies using altered antigens and altered effector T cells.
在过去二十年中，在研究人体肿瘤的免疫反应方面取得了巨大进展。癌细胞蛋白质抗原的鉴定以及在体外和体内引发抗原特异性T细胞反应的更好技术，增进了人们对T细胞识别肿瘤的理解。然而，关于T细胞与肿瘤细胞相互作用的复杂细节仍有许多有待了解。尽管T细胞与靶标之间的相互作用强度被认为是影响T细胞反应的关键因素，但对T细胞亲和力、T细胞受体（TCR）对肽-MHC复合物的亲和力以及对抗原呈递靶标或肿瘤细胞上肽的识别的研究揭示了复杂的关系。与这些研究同时进行的是，已经开发出治疗策略，使用具有改变的肽结构的抗原和通过引入新的抗原结合受体分子修饰的T细胞来增强肿瘤识别。这些策略对T细胞与肿瘤相互作用的深远影响以及这些影响的临床意义，引起了科学家和临床医生的兴趣。近年来，我们大部分工作的重点是肿瘤反应性T细胞的亲和力和效应特性。在此，我们综述该领域的概念和当前结果，以及使用改变的抗原和改变的效应T细胞的治疗策略的意义。
