Division of Molecular Oncology and Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Division of Molecular Oncology and Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Cancer Cell. 2018 Apr 9;33(4):547-562. doi: 10.1016/j.ccell.2018.03.012.
Therapeutic reinvigoration of tumor-specific T cells has greatly improved clinical outcome in cancer. Nevertheless, many patients still do not achieve durable benefit. Recent evidence from studies in murine and human cancer suggest that intratumoral T cells display a broad spectrum of (dys-)functional states, shaped by the multifaceted suppressive signals that occur within the tumor microenvironment. Here we discuss the current understanding of T cell dysfunction in cancer, the value of novel technologies to dissect such dysfunction at the single cell level, and how our emerging understanding of T cell dysfunction may be utilized to develop personalized strategies to restore antitumor immunity.
肿瘤特异性 T 细胞的治疗性再激活极大地改善了癌症的临床疗效。然而,许多患者仍然无法获得持久的受益。最近在鼠类和人类癌症研究中的证据表明,肿瘤内的 T 细胞表现出广泛的(功能失调)功能状态,这些状态由肿瘤微环境中发生的多方面抑制信号所塑造。在这里,我们讨论了目前对癌症中 T 细胞功能障碍的理解,用于在单细胞水平上解析这种功能障碍的新技术的价值,以及我们对 T 细胞功能障碍的理解如何用于开发恢复抗肿瘤免疫的个性化策略。