Liu W Robert, Shipp Margaret A
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Blood. 2017 Nov 23;130(21):2265-2270. doi: 10.1182/blood-2017-06-781989.
Classical Hodgkin lymphoma (cHL) is an unusual B-cell-derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number-dependent increased expression of these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1 receptor-positive immune effectors in the tumor microenvironment and induce PD-1 signaling and associated immune evasion. The genetic bases of enhanced PD-1 signaling in cHL make these tumors uniquely sensitive to PD-1 blockade.
经典型霍奇金淋巴瘤（cHL）是一种罕见的B细胞来源的恶性肿瘤，其中罕见的恶性霍奇金和里德-斯腾伯格（HRS）细胞被广泛但无效的炎症/免疫细胞浸润所包围。这一显著特征表明，恶性HRS细胞逃避免疫监视，并在癌症微环境中与免疫细胞相互作用以实现生存和生长。我们之前发现，cHL具有免疫逃逸的遗传基础：9号染色体p24.1区域以及相关的PD-1配体基因座CD274/PD-L1和PDCD1LG2/PD-L2存在近乎一致的拷贝数改变，且这些配体的表达随拷贝数增加。表达PD-1配体的HRS细胞被认为会与肿瘤微环境中PD-1受体阳性的免疫效应细胞相互作用，诱导PD-1信号传导及相关的免疫逃逸。cHL中增强的PD-1信号传导的遗传基础使得这些肿瘤对PD-1阻断具有独特的敏感性。
