Department of Pathology, Nanfang Hospital, Southern Medical University Guangzhou, China.
The National Key Clinical Specialty, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University Guangzhou, China.
Int J Biol Sci. 2024 Jan 1;20(1):137-151. doi: 10.7150/ijbs.87440. eCollection 2024.
Metastasis and limited benefits of immune checkpoint blockade are two obstacles to the battle against colorectal cancer (CRC). CD73, encoded by the gene 5'-Nucleotidase Ecto (NT5E), is a major enzyme that generates extracellular adenosine. However, whether CD73 affects cancer progression and immune response in CRC remains unclear. Here, the clinical significance of CD73 was assessed in human CRC specimens using immunohistochemistry and bioinformatic analyses. We demonstrated that CD73 is elevated in CRC tissues, particularly in those with metastasis, and correlates with poor prognosis. Gain- and loss-of-function experiments demonstrate that tumor CD73 supports tumor progression and impairs the viability and effector functions of CD8 T cells. Targeting CD73 on CRC cells reduces their malignant phenotypes and improves the anti-cancer response of CD8 T cells in the tumor microenvironment (TME). Moreover, the combination of CD73 blockade and PD-1 inhibitors exhibited enhanced anti-cancer effects when compared to a single-agent treatment. Thus, CD73 may be a promising target in the treatment of CRC.
转移和免疫检查点阻断的有限获益是对抗结直肠癌（CRC）的两个障碍。CD73 由基因 5'-核苷酸酶外切（NT5E）编码，是产生细胞外腺苷的主要酶。然而，CD73 是否影响 CRC 中的癌症进展和免疫反应尚不清楚。在这里，我们使用免疫组织化学和生物信息学分析评估了 CD73 在人类 CRC 标本中的临床意义。我们证明 CD73 在 CRC 组织中上调，特别是在转移的组织中，并且与预后不良相关。增益和失能实验表明，肿瘤 CD73 支持肿瘤进展，并损害 CD8 T 细胞的活力和效应功能。针对 CRC 细胞上的 CD73 可降低其恶性表型，并改善肿瘤微环境（TME）中 CD8 T 细胞的抗癌反应。此外，与单药治疗相比，CD73 阻断和 PD-1 抑制剂的联合治疗显示出增强的抗癌作用。因此，CD73 可能是 CRC 治疗的一个有前途的靶点。
