Fig. 3: LILRB1 deficiency enhances MM cell susceptibility to ferroptosis.

a–f CTR-KD or LILRB1-KD MM cells were treated with ferroptosis inducer RSL3 (400 nM, 4 h-lipid peroxidation, 10 h-cell death)/FIN56 (15 µM, 18-lipid peroxidation, 24h- cell death)/ AA (75 µM, 4h-lipid peroxidation, 10 h-cell death) and ferroptosis inhibitor liproxstatin-1 (lipro, 1 µM). Lipid peroxidation (a, b, e) and cell death (c, d, and f) of CTR-KD or LILRB1-KD MM cells was measured by flow cytometry. g–i NSG mice (female) were injected with 2 × 10⁶ CTR-KD or LILRB1-KD ARP-1 cells through tail vein, followed by administration of vehicle (veh) or ferroptosis inhibitor liproxstatin-1 (lipro, 15 mg/kg, ip) every day and monitoring of tumor burden (CTR-KD, n = 4; LILRB1-KD, n = 4; CTR-KD+liproxstatin-1, n = 7; LILRB1-KD+liproxstatin-1, n = 7). Representative bioluminescent imaging for tumor burden (g) and summarized quantification of bioluminescent imaging (mean ± SE) (h) are shown. i Tumor burden was measured as serum concentration of κ light chain and shown as mean ± SE. j–m CTR- or LILRB1-overexpression MM.1 R cells were treated with ferroptosis inducer RSL3 (400 nM, 4h-lipid peroxidation, 10 h-cell death)/FIN56 (15 µM, 18-lipid peroxidation, 24 h- cell death)/ AA (75 µM, 4 h-lipid peroxidation, 10 h-cell death) and liproxstatin-1 (lipro, 1 µM). Lipid peroxidation (j, l) and cell death (k, m) of CTR-KD or LILRB1-KD MM cells was measured by flow cytometry. n Lipid peroxidation of primary MM patient samples containing subsets of MM cells with different LILRB1 expression was measured. o Gene set enrichment analysis of negative regulation of ferroptosis process genes between LILRB1 high expression MM patients and LILRB1 low expression MM patients in Zhan’s MM 2 dataset. MM patients were sorted by the expression level of LILRB1: the top 100 patients with highest expression of LILRB1 were defined as LILRB1 high expression and the bottom 100 patients with lowest expression were defined as LILRB1 low expression. For (g–i), n, biological repeats, different mice samples. For (a–f, j–m), n, biological repeats, independent experimental samples; data are summary of three independent experimental samples and shown as mean ± SD. Statistical significance was determined by two-tailed Student t-test. Source data are provided as a Source Data file.