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can-22-2483_table_s2.ingenuity_pathway_analysis_of_lilrb3_antibody_treated_u937_cells_suppst2.xlsx (106.72 kB)

Table S2. Ingenuity Pathway Analysis of LILRB3 antibody treated U937 cells from LILRB3 Modulates Acute Myeloid Leukemia Progression and Acts as an Effective Target for CAR T-cell Therapy

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posted on 2023-12-15, 08:40 authored by Sunny Mai, Alan Hodges, Hui-Ming Chen, Jilu Zhang, Yi-Ling Wang, Yongbin Liu, Fumiko Nakatsu, Xiaoxuan Wang, Jing Fang, Yitian Xu, Vitaliy Davidov, Kyeongah Kang, Sai Ravi Pingali, Siddhartha Ganguly, Masataka Suzuki, Marina Konopleva, Brooke Prinzing, Youli Zu, Stephen Gottschalk, Yong Lu, Shu-Hsia Chen, Ping-Ying Pan

Pathway analysis of LILRB3 antibody treated U937 cells.

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Houston Methodist Research Institute (HMRI)

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ARTICLE ABSTRACT

Identifying novel cell surface receptors that regulate leukemia cell differentiation and can be targeted to inhibit cellular proliferation is crucial to improve current treatment modalities in acute myeloid leukemia (AML), especially for relapsed or chemotherapy-refractory leukemia. Leukocyte immunoglobulin-like receptor type B (LILRB) is an immunomodulatory receptor originally found to be expressed in myeloid cells. In this study, we found that LILRB receptors can be induced under inflammatory stimuli and chemotherapy treatment conditions. Blockade of LILRB3 inhibited leukemia cell proliferation and leukemia progression. In addition, treatment with LILRB3 blocking antibodies upregulated myeloid lineage differentiation transcription factors, including PU.1, C/EBP family, and IRF, whereas phosphorylation of proliferation regulators, for example, AKT, cyclin D1, and retinoblastoma protein, was decreased. Conversely, transcriptomic analysis showed LILRB3 activation by agonist antibodies may enhance leukemia survival through upregulation of cholesterol metabolism, which has been shown to promote leukemia cell survival. Moreover, LILRB3-targeted CAR T cells exhibited potent antitumor effects both in vitro and in vivo. Taken together, our results suggest that LILRB3 is a potentially potent target for multiple treatment modalities in AML. LILRB3 regulates differentiation and proliferation in acute myeloid leukemia and can be targeted with monoclonal antibodies and CAR T cells to suppress leukemia growth.

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