Fig. 1. NDV enhances immunogenicity and susceptibility of tumor cells to T cell-mediated killing.

a Expression of IFN-stimulated and pro-inflammatory genes in patient lymphoma samples (MCL and SLL/CLL from blood, FL and DLBCL from lymph nodes) 24 h post infection (p.i.) with NDV; top graph shows percent infected CD19⁺ tumor (analyzed by flow cytometry); the heat map shows the Log₂ fold expression vs ‘No NDV’ (quantitative RT-PCR) (n = 29). b, c Fold expression (vs ‘No NDV’) of MHC and co-stimulatory molecules on (b) patient lymphoma cells (n = 29) 24 h p.i. and (c) SUDHL4 (HLA-ABC, n = 4, CD80, n = 6) and A20 (H2kD, n = 2, CD80, n = 3) cells 24, 48 and 72 h p.i. Repeated measures One-way ANOVA (b) or Two-way ANOVA (c) with Dunnett’s multiple comparisons test. d, e Uninfected/NDV-preinfected GFP⁺ and mCherry⁺ A20 cells (ratio 1:1) were co-cultured with JEDI splenocytes at the indicated ratios. JEDI CD8⁺ T cell activation and tumor cell killing (e) were analyzed after 5 days (n = 3). Repeated measures Two-way ANOVA with Dunnett’s multiple comparisons test. f Uninfected/NDV-preinfected SUDHL4 cells were co-cultured with CD8⁺ T cells in the presence of Blinatumomab (Blina). T cell activation and tumor cell killing (g) were analyzed after 3 days (n = 4). Repeated measures One-way ANOVA with Dunnett’s multiple comparisons test. h GFP⁺ A20 tumor-bearing Balb/c mice were treated with intratumoral NDV and tumors were harvested after 24 h. Representative confocal images are shown (Untr, n = 2; NDV, n = 3). i Intratumoral CD8⁺ T cells from mice treated as in (h) were analyzed by flow cytometry (Untr, n = 5; NDV, n = 4; unpaired, two-tailed t-test). j GFP⁺ A20 tumor-bearing mice were treated with NDV (days 8, 10, 12, 14) and monitored for tumor growth and survival (untreated, n = 12; NDV, n = 11). Log-rank (Mantel-Cox) test. k Intratumoral and TdLN DCs from mice treated as in (h) were analyzed by flow cytometry (Untr, n = 5; NDV, n = 4;, unpaired, two-tailed t-test). Data show mean ± SD. MCL mantle cell lymphoma, SLL small lymphocytic lymphoma, CLL chronic lymphocytic leukemia, FL follicular lymphoma, DLBCL diffuse large B cell lymphoma.