Development of a preclinical model of myeloid tumors with high immune checkpoints expression

作者：D. A. Senichkina, Alena I. Shakirova, Olga S. Epifanovskaya, Ivan Gaponenko, Timofey A. Pyatiizbyantsev, Ekaterina Belotserkovskaya, Anna Malashicheva, Kirill V. Lepik, Ivan Moiseev · 发表于：Oncohematology · 年份：2024 · DOI：10.17650/1818-8346-2024-19-4-131-139 · 被引用次数：2 · 研究领域：Immune Cell Function and Interaction、Acute Myeloid Leukemia Research、Immune cells in cancer

Background. Myelodysplastic syndrome is a group of malignant blood diseases with a high risk of transformation into acute myeloid leukemia. One treatment approach is to target immune checkpoints (ICs) that are overexpressed on tumor cells. To develop these drugs, relevant models are needed for highthroughput screening and study of these biologically active substances, since traditionally used models (mouse and patient biomaterials) are difficult to access, financially and laborintensive, and are characterized by poorly reproducible results.Aim. To develop a model based on a human myeloid cell line with increased expression of L1 and TIM3 to study the activity of ICs inhibitors, the presence of which in the tumor microenvironment in patients with myelodysplastic syndrome and acute myeloid leukemia was associated with a high risk and worse prognosis.Materials and methods. Initial testing of the L1 and TIM3 basal expression level was carried out on cell lines: TH1, HL60, OCIAML2, OCIAML5, KG1, MonoMac1. Induction of IC expression was carried out using interferon γ. Analysis of marker expression was carried out 24 hours after induction of ICs expression and addition of MK2206 using flow cytometry.Results. Basal expression of the studied ICs receptors was absent in all of them, except for KG1; TIM3 was present in 88.4 ± 7.1 % of cells, and L1 – in 88 ± 8.5 %. The addition of interferon γ at a concentration of 50 ng/mL to the MonoMac1 culture led to a significant increase in the pr...