The Harry Perkins Institute of Medical Research, Centre for Medical Research, The University of Western Australia, Nedlands, Western Australia 6009, Australia.
The Harry Perkins Institute of Medical Research, Centre for Medical Research, The University of Western Australia, Nedlands, Western Australia 6009, Australia.
Trends Immunol. 2018 Oct;39(10):801-814. doi: 10.1016/j.it.2018.08.001. Epub 2018 Aug 25.
The density of intratumoral CD8 T cells predicts patient survival and responsiveness to immunotherapy. Effector T cell infiltration in turn is controlled by the tumor vasculature which co-evolves together with an immune-suppressive environment. At the T cell-vascular interface, endothelial cells actively suppress T cell trafficking and function. Conversely, forced activation, normalization, and differentiation of tumor vessels into high endothelial venule entrance portals for lymphocytes can facilitate T cell extravasation. Emerging evidence demonstrates that this process is not exclusively controlled by the endothelium. Indeed, tumor vasculature and CD4 and/or CD8 T cells may regulate each other: increasing local effector T cell numbers or re-invigorating pre-existing T cells via immune checkpoint blockade can directly affect the vasculature. A deeper understanding of the orchestration and duration of this reciprocal relationship may help shape the design of future immunotherapies.
肿瘤内 CD8 T 细胞的密度可预测患者的生存和对免疫疗法的反应。效应 T 细胞的浸润反过来又受到肿瘤血管的控制，而肿瘤血管与免疫抑制环境共同进化。在 T 细胞-血管界面处，内皮细胞积极抑制 T 细胞的迁移和功能。相反，肿瘤血管的强制激活、正常化和分化为淋巴细胞的高内皮静脉入口门，可以促进 T 细胞的渗出。新出现的证据表明，这个过程不仅仅受内皮细胞控制。事实上，肿瘤血管、CD4 和/或 CD8 T 细胞可能会相互调节：增加局部效应 T 细胞数量或通过免疫检查点阻断重新激活预先存在的 T 细胞，可直接影响血管。更深入地了解这种相互关系的协调和持续时间，可能有助于塑造未来免疫疗法的设计。
