Noyori Osamu, Komohara Yoshihiro, Nasser Hesham, Hiyoshi Masateru, Ma Chaoya, Pan Cheng, Carreras Joaquim, Nakamura Naoya, Sato Ai, Ando Kiyoshi, Okuno Yutaka, Nosaka Kisato, Matsuoka Masao, Suzu Shinya
International Research Center for Medical Sciences Joint Research Center for Human Retrovirus Infection Kumamoto University Kumamoto Japan.
Department of Cell Pathology Graduate School of Medical Sciences Kumamoto University Kumamoto Japan.
Clin Transl Immunology. 2019 Aug 13;8(8):e1074. doi: 10.1002/cti2.1074. eCollection 2019.
Infiltration of macrophages through the tyrosine kinase receptor CSF1R is a poor prognosis factor in various solid tumors. Indeed, these tumors produce CSF1R ligand, macrophage colony-stimulating factor (M-CSF) or interleukin-34 (IL-34). However, the significance of these cytokines, particularly, the newly discovered IL-34 in haematological malignancies, is not fully understood. We therefore analysed the role of IL-34 in diffuse large B-cell lymphoma (DLBCL), the most common subtype of malignant lymphoma.
We analysed formalin-fixed paraffin-embedded lymphoma tissues of 135 DLBCL patients for the expression of IL-34 and the number of macrophages, and the survival of these patients. The expression of IL-34 in DLBCL cell lines and the activity of IL-34 to induce the migration of monocytic cells were also characterised.
Several lymphoma tissues showed a clear IL-34 signal, and such signal was detectable in 36% of patients. DLBCL cell lines also expressed IL-34. Interestingly, the percentage of IL-34 patients in the activated B-cell subtype was significantly higher than that in the germinal centre B-cell subtype. More interestingly, IL-34 patients showed shorter survival periods and higher number of macrophages in lymphoma tissues. The recruitment of monocytes is likely the first step for the higher macrophage density in the IL-34 lymphoma tissues. Indeed, IL-34 induced the migration of monocytic cells.
Our results raise the possibility that IL-34 in lymphoma tissues of DLBCL patients recruits monocytes, leading to the higher number of macrophages in the tissues and poor prognosis of patients. IL-34 may be an additional therapeutic target of DLBCL.
巨噬细胞通过酪氨酸激酶受体CSF1R浸润是多种实体瘤预后不良的因素。实际上，这些肿瘤会产生CSF1R配体、巨噬细胞集落刺激因子（M-CSF）或白细胞介素-34（IL-34）。然而，这些细胞因子的意义，尤其是新发现的IL-34在血液系统恶性肿瘤中的意义尚未完全明确。因此，我们分析了IL-34在弥漫性大B细胞淋巴瘤（DLBCL）中的作用，DLBCL是恶性淋巴瘤最常见的亚型。
我们分析了135例DLBCL患者福尔马林固定石蜡包埋的淋巴瘤组织中IL-34的表达、巨噬细胞数量以及这些患者的生存率。还对DLBCL细胞系中IL-34的表达以及IL-34诱导单核细胞迁移的活性进行了表征。
一些淋巴瘤组织显示出清晰的IL-34信号，36%的患者可检测到该信号。DLBCL细胞系也表达IL-34。有趣的是，活化B细胞亚型中IL-34患者的比例显著高于生发中心B细胞亚型。更有趣的是，IL-34患者的生存期较短，淋巴瘤组织中的巨噬细胞数量较多。单核细胞的募集可能是IL-34淋巴瘤组织中巨噬细胞密度较高的第一步。实际上，IL-34可诱导单核细胞迁移。
我们的结果提示，DLBCL患者淋巴瘤组织中的IL-34可能募集单核细胞，导致组织中巨噬细胞数量增加，患者预后不良。IL-34可能是DLBCL的另一个治疗靶点。
Zotero 插件
