Modulation of cytokine production by monocytes and developing‐dendritic cells under the influence of leukemia and lymphoma cell products

Abstract

Cytokines and other soluble factors released by tumor cells play an important role in modulating immune cells to favor tumor development. Monocyte differentiation into macrophages or dendritic cells (DCs) with specific phenotypes is deeply affected by tumor signals and understanding this context is paramount to prevent and propose new therapeutic possibilities. Hence, we developed a study to better describe the modulatory effects of leukemia and lymphoma cell products on human monocytes and monocyte-derived DCs secretion of cytokines such as interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-6, and IL-12. Except with the promyelocytic leukemia cell supernatants (HL-60), the other two tumor supernatants (chronic myeloid leukemia, K562 and Burkitt lymphoma, DAUDI) increased both TNF-α and IL-1β production by monocytes and monocytes undergoing differentiation. This effect was neither explained by alterations of cell number in culture nor by the high amount of vascular endothelial growth factor (VEGF) present in the tumor supernatants. Moreover, all supernatants used were able to induce drastic reduction of IL-12 secretion by cells induced to activation, suggesting a negative interference with Th1 antitumoral responses that should be a huge advantage for tumor progression.

Self-Renewal of Macrophages: Tumor-Released Factors and Signaling Pathways

“…TAMs respond to environmental signals by acquiring a wide spectrum of phenotypic and functional states. Several evidence indicates that, during tumor progression, TAMs predominantly show an M2-like phenotype [ 169 ] and maintain a self-renewal ability [ 63 , 170 , 171 , 172 ], which is correlated with tumor stage malignancy [ 63 ]. The glucose, amino acid, lipid, and iron metabolic profiles of macrophages have all been shown to be altered throughout tumor progression.…”

Tumor-Released Products Promote Bone Marrow-Derived Macrophage Survival and Proliferation

“…Diverse authors have published studies on tumor-derived soluble products and their suppressive effects on myeloid immune cell functions in both human and animal models. The secretion of factors, including prostaglandins, IL-6, IL-10, vascular endothelial growth factor (VEGF), and soluble CD44, as well as products from cell metabolism such as succinate, contributes to the immunosuppression found within the tumor microenvironment [15][16][17][18][19][20]. Macrophages play an important role in tumor progression, with relevant implications for metastasis promotion [21,22].…”