Ferretti Elisa, Hohaus Stefan, Di Napoli Arianna, Belmonte Beatrice, Cuccaro Annarosa, Cupelli Elisa, Galli Eugenio, Rufini Vittoria, Tripodi Gino, Fraternali-Orcioni Giulio, Pistoia Vito, Corcione Anna
Laboratory of Oncology, Istituto Giannina Gaslini, Genova, Italy.
Institute of Hematology, Catholic University of the Sacred Heart, Roma, Italy.
Oncotarget. 2017 Jul 28;8(49):85263-85275. doi: 10.18632/oncotarget.19665. eCollection 2017 Oct 17.
Hodgkin Lymphoma (HL) is a tumor of B-cell origin characterized by Hodgkin and Reed-Stenberg (H/RS) cells embedded in an inflammatory tissue where numerous cytokines/chemokines contribute to shape the microenvironment, leading to the typical clinical symptoms. We investigated: i) the expression of Interleukin-IL-31 (IL-31) and Thymic Stromal Lymphopoietin (TSLP), two Th2-related cytokines with tumor-promoting and pruritogenic functions, and of the respective receptors in HL invaded lymph nodes by flow cytometry, and ii) the potential association of IL-31/TSLP plasma concentrations with clinical characteristics by ELISA. H/RS cells and the major immune cell types infiltrating HL lymph nodes expressed intracytoplasmic and surface IL-31/TSLP, and their receptors. A subgroup of patients showing at diagnosis elevated IL-31 and TSLP plasma levels had an International Prognostic Score>2, indicative of high risk of relapse, and a subsequent positive interim PET-scan, indicative of insufficient response to chemotherapy. No correlation was found between IL-31/TSLP plasma levels and overall or event-free survival. In conclusion, IL-31/TSLP and their receptors are expressed in HL cells and in immune cells infiltrating affected lymph nodes, where both cytokines may contribute to local immune suppression. The clinical impact of IL-31 and TSLP plasma levels has to be further defined in larger patient cohorts.
霍奇金淋巴瘤(HL)是一种起源于B细胞的肿瘤,其特征是霍奇金和里德-斯腾伯格(H/RS)细胞嵌入炎症组织中,众多细胞因子/趋化因子共同塑造了微环境,导致出现典型的临床症状。我们进行了以下研究:i)通过流式细胞术检测白细胞介素-IL-31(IL-31)和胸腺基质淋巴细胞生成素(TSLP)这两种具有促肿瘤和致痒功能的Th2相关细胞因子及其各自受体在HL浸润淋巴结中的表达;ii)通过酶联免疫吸附测定法(ELISA)检测IL-31/TSLP血浆浓度与临床特征之间的潜在关联。H/RS细胞以及浸润HL淋巴结的主要免疫细胞类型均表达细胞质内和表面的IL-31/TSLP及其受体。诊断时IL-31和TSLP血浆水平升高的一组患者国际预后评分>2,表明复发风险高,且随后中期PET扫描呈阳性,表明对化疗反应不足。未发现IL-31/TSLP血浆水平与总生存期或无事件生存期之间存在相关性。总之,IL-31/TSLP及其受体在HL细胞和浸润受累淋巴结中的免疫细胞中表达,这两种细胞因子可能都有助于局部免疫抑制。IL-31和TSLP血浆水平的临床影响有待在更大的患者队列中进一步明确。