Cellini Alessandro, Scarmozzino Federico, Angotzi Francesco, Ruggeri Edoardo, Dei Tos Angelo Paolo, Trentin Livio, Pizzi Marco, Visentin Andrea
Hematology and Clinical Immunology Unit, Department of Medicine, University of Padua, Padua, Italy.
Surgical Pathology and Cytopathology Unit, Department of Medicine, University of Padua, Padua, Italy.
Front Oncol. 2023 May 24;13:1203470. doi: 10.3389/fonc.2023.1203470. eCollection 2023.
Immune evasion is considered one of the modern hallmarks of cancer and is a key element in the pathogenesis of classical Hodgkin Lymphoma (cHL). This haematological cancer achieves effective avoidance of the host's immune system by overexpressing the PD-L1 and PD-L2 proteins on the surface of the neoplastic cells. Subversion of the PD-1/PD-L axis, however, is not the sole contributor to immune evasion in cHL, as the microenvironment nurtured by the Hodgkin/Reed-Sternberg cells is a major player in the creation of a biological niche that sustains their survival and hinders immune recognition. In this review, we will discuss the physiology of the PD-1/PD-L axis and how cHL is able to exploit a plethora of different molecular mechanisms to build an immunosuppressive microenvironment and achieve optimal immune evasion. We will then discuss the success obtained by checkpoint inhibitors (CPI) in treating cHL, both as single agents and as part of combination strategies, analysing the rationale for their combination with traditional chemotherapeutic compounds and the proposed mechanisms of resistance to CPI immunotherapy.
免疫逃逸被认为是癌症的现代特征之一，也是经典型霍奇金淋巴瘤（cHL）发病机制的关键因素。这种血液系统癌症通过在肿瘤细胞表面过度表达PD-L1和PD-L2蛋白，有效地避开了宿主的免疫系统。然而，PD-1/PD-L轴的颠覆并非cHL免疫逃逸的唯一因素，因为霍奇金/里德-斯腾伯格细胞所培育的微环境在创造维持其生存并阻碍免疫识别的生物龛方面起着主要作用。在这篇综述中，我们将讨论PD-1/PD-L轴的生理学，以及cHL如何利用大量不同的分子机制构建免疫抑制微环境并实现最佳免疫逃逸。然后，我们将讨论检查点抑制剂（CPI）在治疗cHL方面取得的成功，包括作为单一药物以及作为联合策略的一部分，分析其与传统化疗药物联合使用的原理以及对CPI免疫治疗的耐药机制。
