Stamm Hauke, Wellbrock Jasmin, Fiedler Walter
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
Mamm Genome. 2018 Dec;29(11-12):694-702. doi: 10.1007/s00335-018-9770-7. Epub 2018 Aug 21.
Avoiding immune surveillance and inducing a tumor-promoting inflammatory milieu found entry into the new generation of the hallmarks of cancer. Cancer cells hijack immune mechanisms which physiologically protect the body from the development of autoimmune diseases and excessive tissue damage during inflammation by downregulating immune responses. This is frequently achieved by upregulation of immune checkpoints. Therefore, the blocking of immune checkpoint ligand-receptor interactions can reinstall the immune systems capability to fight cancer cells as shown for CTLA4 and PD-1 inhibitors in a clinical setting. Newly described checkpoint antigens are currently under investigation in cancer immunotherapy. Preclinical data emphasize the immune checkpoint axis TIGIT-PVR/PVRL2 as very promising target. This axis includes additional receptors such as DNAM-1, CD96, and CD112R. In this review, we discuss the recent findings of the relevance of this complex receptor ligand system in hematologic and solid cancers. Emphasis is also laid on the discussion of potential combinations with other immunotherapeutic approaches.
逃避免疫监视并诱导促肿瘤炎症微环境已成为新一代癌症特征的一部分。癌细胞劫持免疫机制，这些机制在生理上通过下调免疫反应来保护身体免受自身免疫性疾病的发展以及炎症期间过度的组织损伤。这通常通过上调免疫检查点来实现。因此，阻断免疫检查点配体 - 受体相互作用可以恢复免疫系统对抗癌细胞的能力，如在临床环境中CTLA4和PD - 1抑制剂所显示的那样。新描述的检查点抗原目前正在癌症免疫治疗中进行研究。临床前数据强调免疫检查点轴TIGIT - PVR/PVRL2是非常有前景的靶点。该轴包括其他受体，如DNAM - 1、CD96和CD112R。在本综述中，我们讨论了这一复杂受体配体系统在血液系统癌症和实体癌中的相关性的最新发现。同时也着重讨论了与其他免疫治疗方法潜在联合使用的情况。
