Artesunate Switches Monocytes to an Inflammatory Phenotype with the Ability to Kill Leukemic Cells

Autor(es)

Mancuso, Rubia Isler ^[1] ; Olalla Saad, Sara Teresinha ^[1] ; Azambuja, Juliana Hofstatter ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Hematol & Transfus Med Ctr, BR-13083970 Campinas - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 2 JAN 2021.
• Citações Web of Science: 0

Resumo

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 (CD14(high)CD16(-)) with HLA-DR high expression and MCP-1/IL-1 beta 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. (AU)

• Processo FAPESP: 17/21801-2 - Preditores de gravidade e novos tratamentos para neoplasias da medula óssea
• Beneficiário: Sara Teresinha Olalla Saad
• Modalidade de apoio: Auxílio à Pesquisa - Temático