Hematology and Transfusion Medicine Center, University of Campinas, Campinas 13083-970, Brazil.
Int J Mol Sci. 2021 Jan 9;22(2):608. doi: 10.3390/ijms22020608.
Monocytes are components of the tumor microenvironment related to cancer progression and immune escape. Therapeutic strategies for reprogramming monocytes from a tumor-supporting phenotype towards a tumoricidal phenotype are of great interest. Artesunate (ART) may be an interesting option for cancer treatment; however, the role of ART in regulating the inflammatory tumor microenvironment has not yet been investigated. Our aim is to evaluate the immunomodulatory potential of ART in vitro in human primary monocytes. ART treatment induced an increase in inflammatory monocytes (CD14CD16) with HLA-DR high expression and MCP-1/IL-1β release. On the other hand, ART treatment reduced CD206 and CD163 expression, and abolished the monocyte population known as non-classical and intermediate. Leukemia cells in contact with monocytes programmed with ART presented enhanced in vitro apoptosis suggesting that monocytes acquired the ability to kill leukemic cells. ART induced changes in the monocyte phenotype were mediated by JAK2/STAT3 downregulation. The induction of immunosuppressive environment is an important step for cancer progression. ART showed an immunomodulatory activity, leading immune cells to an antitumor phenotype and could be a candidate for immunotherapy in cancer patients.
单核细胞是与癌症进展和免疫逃逸相关的肿瘤微环境的组成部分。将单核细胞从支持肿瘤的表型重编程为杀伤肿瘤的表型的治疗策略引起了极大的兴趣。青蒿琥酯（ART）可能是癌症治疗的一个有趣选择；然而，ART 调节炎症性肿瘤微环境的作用尚未得到研究。我们的目的是评估 ART 在体外对人原代单核细胞的免疫调节潜力。ART 治疗诱导 HLA-DR 高表达和 MCP-1/IL-1β 释放的炎性单核细胞（CD14CD16）增加。另一方面，ART 治疗降低了 CD206 和 CD163 的表达，并消除了称为非经典和中间的单核细胞群体。与经 ART 编程的单核细胞接触的白血病细胞表现出增强的体外凋亡，表明单核细胞获得了杀伤白血病细胞的能力。ART 诱导的单核细胞表型变化是通过 JAK2/STAT3 下调介导的。诱导免疫抑制环境是癌症进展的重要步骤。ART 表现出免疫调节活性，使免疫细胞呈现抗肿瘤表型，可能成为癌症患者免疫治疗的候选药物。
