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.

中文翻译：

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霍奇金淋巴瘤对免疫检查点抑制的主要和获得性耐药机制。

霍奇金淋巴瘤是一种源自B细胞的恶性肿瘤，其特征是在由炎症细胞组成的环境中肿瘤细胞数量少。最近，针对PD-1-PD-L1轴的免疫检查点封锁已显示在复发和难治性霍奇金淋巴瘤患者中取得了巨大成功。但是，完全的反应很少，中位无进展生存期被限制在11-15个月左右。PD-1阻断HL的效率可能取决于CD4 + T细胞，但也涉及肿瘤相关的巨噬细胞（TAM）和NK细胞。这篇综述的目的是强调当前已知的重要的免疫逃避策略，并讨论它们对霍奇金淋巴瘤的免疫检查点阻断的原发性或获得性抗性的可能贡献。这些包括T细胞依赖性机制，例如炎性浸润物的形成，抗原和新抗原的缺乏呈递以及涉及抑制T细胞功能的分子的产生，例如其他免疫检查点，吲哚胺2，3-二加氧酶和腺苷。此外，将讨论NK细胞和TAM在有效的PD-1阻断中的作用。与PD-1平行靶向这些机制可能会提高PD-1阻断疗法的效率。