Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma
Major Histocompatibility Complex Class II and Programmed Death Ligand 1 Expression Predict Outcome After Programmed Death 1 Blockade in Classic Hodgkin Lymphoma
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DOI：
10.1200/jco.2017.77.3994
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发表时间：
2018-04-01
影响因子：
45.3
通讯作者：
Shipp, Margaret A.
中科院分区：
文献类型：
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作者：
Roemer, Margaretha G. M.;Redd, Robert A.;Shipp, Margaret A.
目的霍奇金Reed-Sternberg(HRS)细胞通过多种途径逃避抗肿瘤免疫，包括获得9p24.1/CD274(PD-L1)/PDCD1LG2(PD-L2)和干扰抗原提呈。程序性死亡1(PD-1)受体阻断在经典霍奇金淋巴瘤(CHL)中是有效的，尽管有报道称HRS细胞上缺乏主要组织相容性复合体(MHC)I类表达。在此，我们评估了在CHECKMATE 205试验中接受nivolumab(抗PD-1)治疗的复发/难治性CHL患者对PD-1阻断的敏感性基础。方法用荧光原位杂交方法检测来自档案肿瘤活检组织的HRS细胞9p24.1的改变，并用免疫组织化学方法检测PD配体1(PD-L1)和抗原提呈途径成分2-微球蛋白、MHC I类和MHC II类的表达。这些参数与PD-1阻断后的临床反应和无进展生存期(PFS)相关。结果9p24.1拷贝增加和HRS细胞上PD-L1表达增加的患者具有更好的无进展生存期。HRS细胞表达2-微球蛋白/MHC-I类并不能预测尼伏单抗治疗后的完全缓解或PFS。相反，MHC II类HRS细胞的表达预示着完全缓解。在清髓性自体干细胞移植和nivolumab治疗之间间隔12个月的患者中，MHC-II类HRS细胞的表达与PFS延长相关。结论遗传驱动的PD-L1表达和HRS细胞上MHC-II类阳性是PD-1阻断后预后良好的潜在预测因素。在CHL，对nivolumab的临床反应不依赖于MHC I类HRS细胞的表达。(C)美国临床肿瘤学会2018年
PurposeHodgkin Reed-Sternberg (HRS) cells evade antitumor immunity by multiple means, including gains of 9p24.1/CD274(PD-L1)/PDCD1LG2(PD-L2) and perturbed antigen presentation. Programmed death 1 (PD-1) receptor blockade is active in classic Hodgkin lymphoma (cHL) despite reported deficiencies of major histocompatibility complex (MHC) class I expression on HRS cells. Herein, we assess bases of sensitivity to PD-1 blockade in patients with relapsed/refractory cHL who were treated with nivolumab (anti-PD-1) in the CheckMate 205 trial.MethodsHRS cells from archival tumor biopsies were evaluated for 9p24.1 alterations by fluorescence in situ hybridization and for expression of PD ligand 1 (PD-L1) and the antigen presentation pathway components2-microglobulin, MHC class I, and MHC class IIby immunohistochemistry. These parameters were correlated with clinical responses and progression-free survival (PFS) after PD-1 blockade.ResultsPatients with higher-level 9p24.1 copy gain and increased PD-L1 expression on HRS cells had superior PFS. HRS cell expression of 2-microglobulin/MHC class I was not predictive for complete remission or PFS after nivolumab therapy. In contrast, HRS cell expression of MHC class II was predictive for complete remission. In patients with a > 12-month interval between myeloablative autologous stem-cell transplantation and nivolumab therapy, HRS cell expression of MHC class II was associated with prolonged PFS.ConclusionGenetically driven PD-L1 expression and MHC class II positivity on HRS cells are potential predictors of favorable outcome after PD-1 blockade. In cHL, clinical responses to nivolumab were not dependent on HRS cell expression of MHC class I. (C) 2018 by American Society of Clinical Oncology