Freire-de-Lima Leonardo, Nardy Ana Flávia Fernandes Ribas, Ramos-Junior Erivan Schnaider, Conde Luciana, Santos Lemos Jéssica, da Fonseca Leonardo Marques, Lima Juliana Echevarria, Maiolino Angelo, Morrot Alexandre
Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Institute of Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Front Med (Lausanne). 2017 Jun 27;4:92. doi: 10.3389/fmed.2017.00092. eCollection 2017.
Multiple myeloma (MM) is a plasma cell disorder that still remains incurable. The immune dysfunction of the host is a striking characteristic of MM, leading to tumor growth and reducing the survival rate of patients. Monocytes are precursors of conventional dendritic cells (DCs), a major player in the immunity mechanisms driving protective T cell responses against tumor. Herein, we report that human MM RPMI 8226 cell line shows a pronounced chemoattractant activity for monocytes and also expresses enhanced levels of the leukocyte chemotactic cytokines CXCL12, CCL5, MIP-1β, and CXCL10 in association with elevated levels of both key immunoregulatory interleukins such as IL-4 and IL-10. This cytokine profile was observed together with reduced expression of IFN-γ by MM RPMI 8226 cell line, a determinant interleukin involved in the acquisition of cellular-mediated protective responses against tumor cells. We further demonstrate that MM RPMI 8226 cell line expresses elevated levels of soluble form of the intercellular adhesion molecule-1 known to inhibit antitumoral T cell responses. This attractive modulation of immune responses by MM cells might provide a means to impair early antitumor responses during the establishment of cytokine-mediated immunosuppressive tumor niche.
多发性骨髓瘤(MM)是一种仍无法治愈的浆细胞疾病。宿主的免疫功能障碍是MM的一个显著特征,导致肿瘤生长并降低患者的生存率。单核细胞是传统树突状细胞(DC)的前体,而DC是驱动保护性T细胞针对肿瘤产生应答的免疫机制中的主要参与者。在此,我们报告人MM RPMI 8226细胞系对单核细胞显示出明显的趋化活性,并且与关键免疫调节性白细胞介素如IL-4和IL-10水平升高相关,其白细胞趋化细胞因子CXCL12、CCL5、MIP-1β和CXCL10的表达水平也增强。MM RPMI 8226细胞系还观察到IFN-γ表达降低,IFN-γ是一种决定细胞介导的针对肿瘤细胞的保护性应答获得的白细胞介素。我们进一步证明,MM RPMI 8226细胞系表达的细胞间黏附分子-1可溶性形式水平升高,已知该分子可抑制抗肿瘤T细胞应答。MM细胞对免疫应答的这种有吸引力的调节可能提供了一种在细胞因子介导的免疫抑制性肿瘤微环境建立过程中损害早期抗肿瘤应答的手段。