Expression of the Immune Checkpoint Regulators LAG-3 and TIM-3 in Classical Hodgkin Lymphoma
Expression of the Immune Checkpoint Regulators LAG-3 and TIM-3 in Classical Hodgkin Lymphoma
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DOI：
10.1016/j.clml.2020.11.009
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发表时间：
2021-04-02
影响因子：
2.7
通讯作者：
Ghez, David
中科院分区：
文献类型：
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作者：
El Halabi, Layal;Adam, Julien;Ghez, David
程序性细胞死亡1（PD-1）/程序性死亡配体1（PD-L1）阻断剂用于复发/难治性经典霍奇金淋巴瘤（HL），而其他免疫检查点，如淋巴细胞活化基因3（LAG-3）和T细胞免疫球蛋白和含粘蛋白结构域3（TIM-3）也可能发挥作用。通过对57例活检标本进行免疫组化，我们发现TIM-3在36%的病例中由霍奇金和里德/斯滕贝格细胞表达，LAG-3和TIM-3在肿瘤微环境中广泛表达。LAG-3和TIM-3可能构成治疗HL的治疗靶点。引言：程序性细胞死亡1（PD-1）/程序性死亡配体1（PD-L1）轴的作用在经典霍奇金淋巴瘤（HL）中得到了很好的确立，其中PD-1阻断在复发性/难治性疾病中表现出惊人的疗效。然而，对HL样本中其他免疫检查点的频率和细胞分布知之甚少。患者和方法：我们使用免疫组织化学方法，沿着PD-1和PD-L1，研究了57例经典HL患者活检样本中淋巴细胞活化基因3（LAG-3）和T细胞免疫球蛋白和含粘蛋白结构域3（TIM-3）的表达。结果：几乎所有病例的Hodgkin和Reed/斯滕贝格（HRS）细胞均为PD-L1强阳性。HRS细胞在36%的样品中为TIM-3阳性，而LAG-3很少表达（5.2%）。在微环境中，PD-1、LAG-3和TIM-3分别在65%、98%和96%的病例中由>= 5%的细胞表达。HRS细胞周围的T细胞群由表达PD-1和LAG-3的CD 4（+）FoxP 3辅助T细胞组成，TIM-3的表达可变。结论：本研究首次证明LAG-3和TIM-3几乎总是在经典HL的微环境中表达。这可能构成靶向LAG-3或TIM-3与抗PD-1抗体联合治疗复发性/难治性HL的基础。(C)2020爱思唯尔公司All rights reserved.
Programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) blocking agents are used in relapsed/ refractory classical Hodgkin lymphoma (HL), while other immune checkpoints such as lymphocyte-activation gene 3 (LAG-3) and T-cell immunoglobulin and mucin-domain containing 3 (TIM-3) may also play a role. By performing immunohistochemistry on 57 biopsy samples, we found that TIM-3 was expressed by Hodgkin and Reed/Sternberg cells in 36% of the cases, and LAG-3 and TIM-3 were widely expressed in the tumor microenvironment. LAG-3 and TIM-3 may constitute therapeutic targets in the treatment of HL.Introduction: The role of the programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) axis is well established in classical Hodgkin lymphoma (HL), where PD-1 blockade demonstrated spectacular efficacy in relapsed/ refractory disease. However, little is known about the frequency and cellular distribution of other immune checkpoints in HL samples. Patients and Methods: Using immunohistochemistry, we investigated, along with PD-L1 and PD-1, the expression of lymphocyte-activation gene 3 (LAG-3) and T-cell immunoglobulin and mucin-domain containing 3 (TIM-3) in 57 biopsy samples of patients with classical HL. Results: Hodgkin and Reed/Sternberg (HRS) cells were strongly positive for PD-L1 in nearly all cases. HRS cells were TIM-3 positive in 36% of samples, whereas LAG-3 was rarely expressed (5.2%). In the microenvironment, PD-1, LAG-3, and TIM-3 were expressed by >= 5% of cells in 65%, 98%, and 96% of cases, respectively. T-cell rosettes surrounding HRS cells consisted of CD4(+) FoxP3 helper T cells expressing both PD-1 and LAG-3, with a variable expression of TIM-3. Conclusion: This study demonstrates for the first time that LAG-3 and TIM-3 are nearly always expressed in the microenvironment of classical HL. This may constitute the basis for targeting LAG-3 or TIM-3 in combination with anti-PD-1 antibodies in the treatment of relapsed/refractory HL. (C) 2020 Elsevier Inc. All rights reserved.