Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
PLoS One. 2019 Nov 12;14(11):e0224621. doi: 10.1371/journal.pone.0224621. eCollection 2019.
Classic Hodgkin lymphoma (CHL) characteristically shows few malignant cells in a microenvironment comprised of mixed inflammatory cells. Although CHL is associated with a high cure rate, recent studies have associated poor prognosis with absolute monocyte count in peripheral blood and increased monocyte/macrophages in involved lymph nodes. Thus, the role of monocytic infiltration and macrophage differentiation in the tumor microenvironment of CHL may be more relevant than absolute macrophage numbers to defining prognosis in CHL patients and potentially have therapeutic implications. Most studies identify tumor-associated macrophages (TAMs) using markers (e.g., CD68) expressed by macrophages and other mononuclear phagocytes, such as monocytes. In contrast, Class A Scavenger Receptor (SR-A/CD204) is expressed by tissue macrophages but not monocytic precursors. In this study, we examined SR-A expression in CHL (n = 43), and compared its expression with that of other macrophage markers. We confirmed a high prevalence of mononuclear cells that stained with CD68, CD163, and CD14 in CHL lymph nodes. However, SR-A protein expression determined by immunohistochemistry was limited to macrophages localized in sclerotic bands characteristic of nodular sclerosis CHL. In contrast, SR-A protein was readily detectable in lymph nodes with metastatic tumor, extra-nodal CHL, T cell/histiocyte-rich large B cell lymphoma, and resident macrophages in non-malignant tissues, including spleen, lymph node, liver and lung. The results of SR-A protein expression paralleled the expression of SR-A mRNA determined by quantitative RT-PCR. These data provide evidence that tumor-infiltrating monocyte/macrophages in CHL have a unique phenotype that likely depends on the microenvironment of nodal CHL.
经典霍奇金淋巴瘤 (CHL) 表现为在由混合炎症细胞组成的微环境中存在少数恶性细胞。尽管 CHL 的治愈率很高，但最近的研究表明，外周血绝对单核细胞计数增加和受累淋巴结中单核细胞/巨噬细胞增加与预后不良相关。因此，单核细胞浸润和巨噬细胞分化在 CHL 肿瘤微环境中的作用可能比巨噬细胞数量对 CHL 患者的预后更相关，并且可能具有治疗意义。大多数研究使用标记物（例如 CD68）来识别肿瘤相关巨噬细胞 (TAMs)，这些标记物表达于巨噬细胞和其他单核吞噬细胞，如单核细胞。相比之下，A 类清道夫受体 (SR-A/CD204) 仅表达于组织巨噬细胞，而不表达于单核细胞前体。在这项研究中，我们研究了 CHL 中的 SR-A 表达，并将其表达与其他巨噬细胞标记物进行了比较。我们证实了在 CHL 淋巴结中存在大量单核细胞，这些细胞用 CD68、CD163 和 CD14 染色。然而，通过免疫组织化学确定的 SR-A 蛋白表达仅限于结节性硬化 CHL 特征性硬化带中定位的巨噬细胞。相比之下，SR-A 蛋白在具有转移性肿瘤、结外 CHL、T 细胞/组织细胞丰富的大 B 细胞淋巴瘤和非恶性组织（包括脾脏、淋巴结、肝脏和肺部）中的常驻巨噬细胞中很容易检测到。SR-A 蛋白表达的结果与定量 RT-PCR 确定的 SR-A mRNA 表达相平行。这些数据提供了证据，表明 CHL 中的肿瘤浸润性单核细胞/巨噬细胞具有独特的表型，可能取决于淋巴结 CHL 的微环境。
