TP53 loss in lymphoma cells impairs macrophage ability to phagocytose tumor B cells. (A) Schematic representation of an ADCP assay. (B) Alemtuzumab (anti-CD52)-mediated ADCP of empty vector (shCTRL) and the indicated DDR-knockdown hMB cells, pretreated or not with 3 µM mafosfamide (CTX) and cocultured with peritoneal macrophages (3 independent experiments, 5 replicates per experiment). (C) ADCP percent of shCTRL hMB cells, pretreated or not with nutlin-3A (left panel) (n = 3). Right panel shows ADCP fold change (FC) induced upon nutlin-3A pretreatment on the indicated DDR-knockdown hMB cells (n = 3). (D) ADCP assay of CLL cells from patients with TP53 WT and mutant expression (TP53 mut) on the presence of peritoneal macrophages and alemtuzumab (left) or mCherry⁺ J77A4.1 macrophages and 10 mg rituximab and 3 µM mafosfamide (n = 6) or J77A4.1 macrophages (n = 15). (E) Daratumumab (anti-CD38 antibody)-mediated ADCP of multiple myeloma (MM) tumor cells obtained from patients with normal TP53 expression (normal karyotype or 13q14 deletion) and from patients with TP53 deletion. Tumor cells were cocultured with autologous macrophages in the indicated ratios (10:1 ratio, del13q14DEL vs TP53DEL P = .025; n = 3). (F) Eµ-TCL1/wt and Eµ-TCL1/Tp53^fl/fl leukemic mice were treated or not with 10 mg/kg cyclophosphamide (CTX) for 24 hours. Then, the spleen leukemic cells were isolated and used to perform an ADCP in the presence of peritoneal macrophages (n = 5-7). (G) Kaplan-Meier analysis comparing the survival of shCTRL and shTP53 hMB–transplanted nonobese diabetes scid gamma mice receiving cyclophosphamide and alemtuzumab (CA) as CIT combination. PBS was used as control. The treatment was given IP 10 days after IV hMB cell injection (n = 5-6). (*P < .05, **P ≤ .01). IP, intraperitoneal.