Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9700RB Groningen, the Netherlands.
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9700RB Groningen, the Netherlands.
Cancer Treat Rev. 2020 Jan;82:101931. doi: 10.1016/j.ctrv.2019.101931. Epub 2019 Nov 11.
Hodgkin lymphoma is a B cell derived malignancy characterized by a low number of tumor cells within an environment consisting of inflammatory cells. Recently, immune checkpoint blockade targeting the PD-1-PD-L1 axis has shown to be a great success in relapsed and refractory Hodgkin lymphoma patients. However, complete responses are scarce and median progression-free survival is limited to around 11-15 months. Efficiency of PD-1 blockade in HL might be dependent on CD4+ T cells, but also tumor associated macrophages (TAMs) and NK cells are implicated. The aim of this review is to highlight currently known prominent immune evasion strategies and discuss their possible contribution to primary or acquired resistance to immune checkpoint blockade in Hodgkin lymphoma. These include T cell dependent mechanisms such as shaping of the inflammatory infiltrate, lack of presentation of antigens and neoantigens and production of molecules involved in suppression of T cell functionality such as other immune checkpoints, indoleamine 2,3-dioxygenase and adenosine. Moreover, the role of NK cells and TAMs in efficient PD-1 blockade will be discussed. Targeting these mechanisms in parallel to PD-1 may potentially increase efficiency of PD-1 blockade therapy.
霍奇金淋巴瘤是一种 B 细胞来源的恶性肿瘤，其特征是肿瘤细胞数量较少，而在肿瘤微环境中存在大量炎症细胞。最近，针对 PD-1-PD-L1 轴的免疫检查点阻断在复发性和难治性霍奇金淋巴瘤患者中显示出巨大的成功。然而，完全缓解的情况很少见，无进展生存期的中位数仅为 11-15 个月左右。PD-1 阻断在 HL 中的效率可能依赖于 CD4+ T 细胞，但肿瘤相关巨噬细胞（TAMs）和 NK 细胞也参与其中。本综述旨在强调目前已知的主要免疫逃逸策略，并讨论它们可能对霍奇金淋巴瘤中对免疫检查点阻断的原发性或获得性耐药的贡献。这些机制包括 T 细胞依赖性机制，如炎症浸润的形成、抗原和新抗原的呈递缺失以及参与抑制 T 细胞功能的分子的产生，如其他免疫检查点、吲哚胺 2,3-双加氧酶和腺苷。此外，还将讨论 NK 细胞和 TAMs 在有效 PD-1 阻断中的作用。同时针对这些机制进行靶向治疗可能会潜在地提高 PD-1 阻断治疗的效率。
