Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano (PN), Italy.
Int J Mol Sci. 2019 May 15;20(10):2416. doi: 10.3390/ijms20102416.
Classic Hodgkin lymphoma (cHL) is characterized by a few tumor cells surrounded by a protective, immunosuppressive tumor microenvironment composed of normal cells that are an active part of the disease. Hodgkin and Reed-Sternberg (HRS) cells evade the immune system through a variety of different mechanisms. They evade antitumor effector T cells and natural killer cells and promote T cell exhaustion. Using cytokines and extracellular vesicles, they recruit normal cells, induce their proliferation and "educate" (i.e. reprogram) them to become immunosuppressive and protumorigenic. Therefore, alternative treatment strategies are being developed to target not only tumor cells but also the tumor microenvironment. Here we summarize current knowledge on the ability of HRS cells to build their microenvironment and to educate normal cells to become immunosuppressive. We also describe therapeutic strategies to counteract formation of the tumor microenvironment and related processes leading to T cell exhaustion and repolarization of immunosuppressive tumor-associated macrophages.
经典霍奇金淋巴瘤 (cHL) 的特征是少数肿瘤细胞被保护性的免疫抑制肿瘤微环境包围，该微环境由正常细胞组成，是疾病的一个活跃组成部分。霍奇金和里德-斯特恩伯格 (HRS) 细胞通过多种不同的机制逃避免疫系统。它们逃避抗肿瘤效应 T 细胞和自然杀伤细胞，并促进 T 细胞衰竭。利用细胞因子和细胞外囊泡，它们招募正常细胞，诱导其增殖并“教育”（即重新编程）它们成为免疫抑制和促肿瘤的。因此，正在开发替代治疗策略，不仅针对肿瘤细胞，还针对肿瘤微环境。在这里，我们总结了 HRS 细胞构建微环境和教育正常细胞成为免疫抑制的能力的最新知识。我们还描述了对抗肿瘤微环境形成以及导致 T 细胞衰竭和免疫抑制肿瘤相关巨噬细胞重新极化的相关过程的治疗策略。
