Ferrarini Isacco, Rigo Antonella, Visco Carlo, Krampera Mauro, Vinante Fabrizio
Section of Hematology, Department of Medicine, University of Verona, 37134 Verona, Italy.
Cancer Research and Cell Biology Laboratory, Department of Medicine, University of Verona, 37134 Verona, Italy.
Cancers (Basel). 2020 Dec 14;12(12):3757. doi: 10.3390/cancers12123757.
Classic Hodgkin lymphoma (cHL) is a unique lymphoid neoplasm characterized by extensive immune infiltrates surrounding rare malignant Hodgkin Reed-Sternberg (HRS) cells. Different subsets of T and NK cells have long been recognized in the cHL microenvironment, yet their distinct contribution to disease pathogenesis has remained enigmatic. Very recently, novel platforms for high dimensional analysis of immune cells, such as single-cell RNA sequencing and mass cytometry, have revealed unanticipated insights into the composition of T- and NK-cell compartments in cHL. Advances in imaging techniques have better defined specific T-helper subpopulations physically interacting with neoplastic cells. In addition, the identification of novel cytotoxic subsets with an exhausted phenotype, typically enriched in cHL milieu, is shedding light on previously unrecognized immune evasion mechanisms. This review examines the immunological features and the functional properties of T and NK subsets recently identified in the cHL microenvironment, highlighting their pathological interplay with HRS cells. We also discuss how this knowledge can be exploited to predict response to immunotherapy and to design novel strategies to improve PD-1 blockade efficacy.
经典型霍奇金淋巴瘤（cHL）是一种独特的淋巴样肿瘤，其特征是在罕见的恶性霍奇金-里德-斯腾伯格（HRS）细胞周围有广泛的免疫浸润。长期以来，人们在cHL微环境中已识别出不同的T细胞和自然杀伤（NK）细胞亚群，但它们对疾病发病机制的独特贡献仍不明确。最近，诸如单细胞RNA测序和质谱细胞术等用于免疫细胞高维分析的新平台，揭示了cHL中T细胞和NK细胞区室组成方面意想不到的见解。成像技术的进步更好地界定了与肿瘤细胞发生物理相互作用的特定辅助性T细胞亚群。此外，对通常在cHL环境中富集的具有耗竭表型的新型细胞毒性亚群的识别，正在揭示此前未被认识的免疫逃逸机制。本综述探讨了最近在cHL微环境中识别出的T细胞和NK细胞亚群的免疫学特征及功能特性，强调了它们与HRS细胞的病理相互作用。我们还讨论了如何利用这些知识来预测免疫治疗反应，并设计新策略以提高程序性死亡蛋白1（PD-1）阻断疗法的疗效。
