Eppler Elisabeth, Janas Eva, Link Karl, Weidmann Lukas, Bischofberger Helena, Wenger Michael, Tinguely Marianne, Schraml Peter, Moch Holger, Fellbaum Christian
Research Group Neuro-endocrine-immune Interactions, Institute of Anatomy, University of Zurich, Zurich, Switzerland,
Cell Tissue Res. 2015 Mar;359(3):841-51. doi: 10.1007/s00441-014-2052-0. Epub 2014 Dec 9.
Hodgkin's lymphoma (HL) is among the most frequent nodal lymphomas in the Western world and is classified into two disease entities: nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) and classical Hodgkin's lymphoma (cHL, 95% of all HL). HL lesions are characterised by a minority of clonal neoplastic cells, namely Hodgkin and Reed-Sternberg (HRS) cells and their variants in cHL and lymphocyte-predominant (LP) cells in NLPHL, both occurring within a microenvironment of, for example, reactive T and B cells, macrophages and granulocytes that are assumed to support the proliferation and maintenance of neoplastic cells through cytokines, chemokines and growth factors. Insulin-like growth factor I (IGF-I) is an important growth factor involved in proliferation, differentiation, apoptosis and cell survival of numerous (including immune) tissues and probably has a role in tumour pathogenesis and maintenance. Although HL is characterised by disturbed cell differentiation and apoptosis mechanisms, with the involvement of the IGF-I receptor (IGF-1R), the distinct location of IGF-I in HL has not yet been defined. We localise IGF-I by double-immunofluorescence in frequent neoplastic cells of all cHL and NLPHL cases investigated. Additionally, IGF-I immunoreactivity is detected in high endothelial venules and various immune cells within the surrounding tissue of cHL including neutrophils and macrophages. IGF-1R immunoreactivity of variable intensity is found in HRS cells and high endothelial venules within the microenvironment in cHL. We assume that autocrine and paracrine IGF-I plays an anti-apoptotic role in tumour pathogenesis and in shaping the tumour microenvironment.
霍奇金淋巴瘤（HL）是西方世界最常见的淋巴结淋巴瘤之一，可分为两种疾病实体：结节性淋巴细胞为主型霍奇金淋巴瘤（NLPHL）和经典型霍奇金淋巴瘤（cHL，占所有HL的95%）。HL病变的特征是少数克隆性肿瘤细胞，即cHL中的霍奇金和里德-斯腾伯格（HRS）细胞及其变体，以及NLPHL中的淋巴细胞为主型（LP）细胞，它们都存在于例如反应性T细胞和B细胞、巨噬细胞和粒细胞的微环境中，这些细胞被认为通过细胞因子、趋化因子和生长因子支持肿瘤细胞的增殖和维持。胰岛素样生长因子I（IGF-I）是一种重要的生长因子，参与众多（包括免疫）组织的增殖、分化、凋亡和细胞存活，可能在肿瘤发病机制和维持中起作用。尽管HL的特征是细胞分化和凋亡机制紊乱，涉及IGF-I受体（IGF-1R），但IGF-I在HL中的具体定位尚未明确。我们通过双重免疫荧光在所有研究的cHL和NLPHL病例的常见肿瘤细胞中定位IGF-I。此外，在cHL周围组织的高内皮小静脉和各种免疫细胞（包括中性粒细胞和巨噬细胞）中检测到IGF-I免疫反应性。在cHL微环境中的HRS细胞和高内皮小静脉中发现了强度可变的IGF-1R免疫反应性。我们认为自分泌和旁分泌的IGF-I在肿瘤发病机制和塑造肿瘤微环境中起抗凋亡作用。
