Department of Experimental Oncology 2, Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano, PN, Italy.
J Pathol. 2010 Jul;221(3):248-63. doi: 10.1002/path.2711.
It has become clear that cancer is not merely a growth of autonomously proliferating cells, but that other non-malignant cell types are a functional part of the disease. Immune cells, fibroblasts, specialized mesenchymal cells and microvasculature together make up the tumour microenvironment and have functional interactions with tumour cells. Classical Hodgkin's lymphoma (cHL) is characterized by only a few malignant cells and an abundance of inflammatory cells. Hodgkin and Reed-Sternberg (HRS) cells are surrounded by T and B cells admixed with plasma cells, macrophages, eosinophils and mast cells. A constitutive activity of NF-kappaB and an altered JAK-STAT signalling pathway are part of the biological background associated with the increased expression of cytokines and cytokine receptors seen in HRS cells. Over-expression of the members of the TNF receptor family, especially CD30 and CD40, is a hallmark of HRS cells. cHL is a tumour where aberrant cytokine production contributes not only to the proliferation of HRS cells but also to the maintenance of an appropriate environment for the tumour cells. In addition, several chemokines contribute to the composition of the inflammatory background in cHL. This review summarizes updated information on the complex interactions between the HRS cells and their tissue microenvironment and highlights the development of newer therapeutic strategies aimed at targeting the non-malignant inflammatory/immune cellular components of HL that are involved in cancer cell growth and/or immune escape.
已经清楚的是，癌症不仅仅是自主增殖细胞的生长，其他非恶性细胞类型也是疾病的一个功能部分。免疫细胞、成纤维细胞、专门的间充质细胞和微血管共同构成肿瘤微环境，并与肿瘤细胞发生功能相互作用。经典霍奇金淋巴瘤（cHL）的特征是仅有少数恶性细胞和大量炎症细胞。Hodgkin 和 Reed-Sternberg（HRS）细胞被 T 和 B 细胞包围，其中混合有浆细胞、巨噬细胞、嗜酸性粒细胞和肥大细胞。NF-κB 的组成活性和改变的 JAK-STAT 信号通路是与 HRS 细胞中观察到的细胞因子和细胞因子受体表达增加相关的生物学背景的一部分。TNF 受体家族成员的过度表达，特别是 CD30 和 CD40，是 HRS 细胞的一个标志。cHL 是一种肿瘤，其中异常的细胞因子产生不仅有助于 HRS 细胞的增殖，而且有助于为肿瘤细胞维持适当的环境。此外，几种趋化因子有助于 cHL 中炎症背景的组成。这篇综述总结了关于 HRS 细胞与其组织微环境之间复杂相互作用的最新信息，并强调了开发针对 HL 中涉及癌细胞生长和/或免疫逃避的非恶性炎症/免疫细胞成分的新型治疗策略的发展。
