癌症免疫学中的树突状细胞。
Dendritic cells in cancer immunology.
机构信息
Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, 63110, USA.
出版信息
Cell Mol Immunol. 2022 Jan;19(1):3-13. doi: 10.1038/s41423-021-00741-5. Epub 2021 Sep 3.
The clinical success of immune checkpoint therapy (ICT) has produced explosive growth in tumor immunology research because ICT was discovered through basic studies of immune regulation. Much of the current translational efforts are aimed at enhancing ICT by identifying therapeutic targets that synergize with CTLA4 or PD1/PD-L1 blockade and are solidly developed on the basis of currently accepted principles. Expanding these principles through continuous basic research may help broaden translational efforts. With this mindset, we focused this review on three threads of basic research directly relating to mechanisms underlying ICT. Specifically, this review covers three aspects of dendritic cell (DC) biology connected with antitumor immune responses but are not specifically oriented toward therapeutic use. First, we review recent advances in the development of the cDC1 subset of DCs, identifying important features distinguishing these cells from other types of DCs. Second, we review the antigen-processing pathway called cross-presentation, which was discovered in the mid-1970s and remains an enigma. This pathway serves an essential in vivo function unique to cDC1s and may be both a physiologic bottleneck and therapeutic target. Finally, we review the longstanding field of helper cells and the related area of DC licensing, in which CD4 T cells influence the strength or quality of CD8 T cell responses. Each topic is connected with ICT in some manner but is also a fundamental aspect of cell-mediated immunity directed toward intracellular pathogens.
免疫检查点治疗 (ICT) 的临床成功推动了肿瘤免疫学研究的爆炸式增长,因为 ICT 是通过对免疫调节的基础研究发现的。目前的许多转化努力旨在通过确定与 CTLA4 或 PD1/PD-L1 阻断协同作用的治疗靶点来增强 ICT,并在当前公认的原则基础上进行扎实的开发。通过持续的基础研究扩展这些原则可能有助于拓宽转化工作。基于这种思路,我们将本综述的重点放在与 ICT 机制直接相关的三个基础研究线索上。具体来说,本综述涵盖了与抗肿瘤免疫反应相关的三个方面的树突状细胞 (DC) 生物学,但并非专门针对治疗用途。首先,我们回顾了 DC 中 cDC1 亚群的最新进展,确定了这些细胞与其他类型 DC 区分开来的重要特征。其次,我们回顾了称为交叉呈递的抗原加工途径,该途径于 20 世纪 70 年代中期被发现,至今仍是一个谜。该途径在 cDC1 中发挥着独特的体内功能,可能既是生理瓶颈也是治疗靶点。最后,我们回顾了辅助细胞的长期领域和 DC 许可的相关领域,其中 CD4 T 细胞影响 CD8 T 细胞反应的强度或质量。每个主题都以某种方式与 ICT 相关联,但也是针对细胞内病原体的细胞介导免疫的基本方面。