Immunology in Cancer and Infection Laboratory and.
Medical Genomics, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
J Clin Invest. 2018 Jun 1;128(6):2613-2625. doi: 10.1172/JCI98769. Epub 2018 May 14.
Critical immune-suppressive pathways beyond programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) require greater attention. Nectins and nectin-like molecules might be promising targets for immunotherapy, since they play critical roles in cell proliferation and migration and exert immunomodulatory functions in pathophysiological conditions. Here, we show CD155 expression in both malignant cells and tumor-infiltrating myeloid cells in humans and mice. Cd155-/- mice displayed reduced tumor growth and metastasis via DNAM-1 upregulation and enhanced effector function of CD8+ T and NK cells, respectively. CD155-deleted tumor cells also displayed slower tumor growth and reduced metastases, demonstrating the importance of a tumor-intrinsic role of CD155. CD155 absence on host and tumor cells exerted an even greater inhibition of tumor growth and metastasis. Blockade of PD-1 or both PD-1 and CTLA4 was more effective in settings in which CD155 was limiting, suggesting the clinical potential of cotargeting PD-L1 and CD155 function.
需要更加关注超越程序性死亡 1（PD-1）和程序性死亡配体 1（PD-L1）的关键免疫抑制途径。黏附分子和黏附样分子可能是免疫治疗的有前途的靶点，因为它们在细胞增殖和迁移中发挥关键作用，并在病理生理条件下发挥免疫调节功能。在这里，我们在人和小鼠的恶性细胞和肿瘤浸润髓样细胞中均显示 CD155 的表达。通过 DNAM-1 的上调和增强 CD8+T 和 NK 细胞的效应功能，Cd155-/-小鼠显示出肿瘤生长和转移的减少。CD155 缺失的肿瘤细胞也显示出较慢的肿瘤生长和减少转移，表明 CD155 在肿瘤内在中的重要作用。宿主和肿瘤细胞上缺乏 CD155 对肿瘤生长和转移的抑制作用更大。在 CD155 受到限制的情况下，阻断 PD-1 或 PD-1 和 CTLA4 更为有效，这表明同时靶向 PD-L1 和 CD155 功能的临床潜力。
