Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA; email:
University of Texas Health Science Center at Houston Graduate School of Biomedical Science, Houston, Texas 77054, USA.
Annu Rev Med. 2019 Jan 27;70:409-424. doi: 10.1146/annurev-med-050217-121900. Epub 2018 Oct 31.
The driver and passenger mutations accumulated in the process of malignant transformation offer an adequate spectrum of immune visible alterations to the cellular proteome and resulting peptidome to render these cancers targetable-and, in theory, rejectable-by the host T cell immune response. In addition, cancers often overexpress tissue-specific and developmental antigens to which immune tolerance is incomplete. Sometimes, virally transferred oncogenes drive malignant transformation and remain expressed throughout the cancer. Despite this state of antigenic sufficiency, cancer grows progressively and overcomes all efforts of the host immune system to contain it. While therapeutic cancer vaccination can mobilize high frequencies of tumor-specific T cells, these responses remain subject to intratumoral attenuation. Antibody modulation of T cell function through checkpoint blockade or costimulatory activation can restore survival, proliferation, and effector function to these tumor-infiltrating T cells and convert otherwise subtherapeutic vaccines into potentially curative cancer immunotherapeutics.
在恶性转化过程中积累的驱动突变和乘客突变，为细胞蛋白质组和由此产生的肽组提供了充分的免疫可见改变，使这些癌症成为宿主 T 细胞免疫反应的靶标-而且，从理论上讲，是可以被拒绝的。此外，癌症通常过度表达组织特异性和发育性抗原，而这些抗原的免疫耐受性不完全。有时，病毒转移的癌基因驱动恶性转化并在整个癌症中持续表达。尽管处于抗原充足的状态，但癌症仍在不断进展，并克服了宿主免疫系统控制它的所有努力。虽然治疗性癌症疫苗接种可以动员高频率的肿瘤特异性 T 细胞，但这些反应仍然受到肿瘤内衰减的影响。通过检查点阻断或共刺激激活来调节抗体对 T 细胞功能的作用，可以恢复这些肿瘤浸润 T 细胞的存活、增殖和效应功能，并将原本疗效不佳的疫苗转化为潜在的治愈性癌症免疫疗法。
