Ansell Stephen M
From the Division of Hematology, Mayo Clinic, Rochester, MN.
Cancer J. 2018 Sep/Oct;24(5):249-253. doi: 10.1097/PPO.0000000000000331.
Classic Hodgkin lymphoma has a unique tumor composition in that there is a paucity of malignant cells present, and most of the tumor consists of normal immune and stromal cells. Despite the presence of an immune infiltrate within the tumor microenvironment, the malignant cells effectively evade the immune system and appear to utilize the presence of immune cells to promote the growth and survival of Hodgkin-Reed-Sternberg cells. Hodgkin-Reed-Sternberg cells evade immune detection because of overexpression of programmed death 1 ligands, PD-L1 and PD-L2, which suppress T-cell activation, and loss of expression of major histocompatibility complex molecules that prevent effective immune recognition. Recognition of these immune defects has led to clinical use of immune checkpoint blockade in classic Hodgkin lymphoma. Clinical trials using antibodies that block programmed death 1/PD-L1 signaling have shown remarkable responses to therapy and have led to the approval of nivolumab and pembrolizumab for use in patients with relapsed and refractory disease. Trials are currently testing immune checkpoint blockade in earlier lines of therapy.
经典型霍奇金淋巴瘤具有独特的肿瘤组成，即存在的恶性细胞很少，且大部分肿瘤由正常免疫细胞和基质细胞组成。尽管肿瘤微环境中有免疫浸润，但恶性细胞有效地逃避免疫系统，并似乎利用免疫细胞的存在来促进霍奇金-里德-斯腾伯格细胞的生长和存活。霍奇金-里德-斯腾伯格细胞由于程序性死亡1配体PD-L1和PD-L2的过度表达（其抑制T细胞活化）以及主要组织相容性复合体分子表达的缺失（这阻止了有效的免疫识别）而逃避免疫检测。对这些免疫缺陷的认识已导致免疫检查点阻断在经典型霍奇金淋巴瘤中的临床应用。使用阻断程序性死亡1/PD-L1信号传导的抗体进行的临床试验已显示出对治疗的显著反应，并已导致纳武单抗和派姆单抗被批准用于复发和难治性疾病患者。目前正在进行试验，测试免疫检查点阻断在更早期治疗方案中的效果。
