Fig. 6: 225Ac-NM600 + ICI showed therapeutic benefit over 90Y-NM600 + ICI and did not decrease immune cell populations in immune-resistant tumors.
A–C Myc-CaP tumor-bearing mice received the indicated treatment. A Experimental scheme. Tumor growth (B) and overall survival (C) are shown. D–H Single cell RNA sequencing of B78 tumors. D Cell type fractions in lymphoid compartment. Cell types having >5% fraction in at least one sample are represented. E Single cell RNA sequencing treatment scheme. B78 tumor-bearing mice received either 2 Gy 90Y-, 177Lu-, 225Ac-NM600 or EBRT + ICI (anti-CTLA4 and anti-PD-L1) on days −3/0/3 or ICI alone. Tumors were harvested on day 15, dissociated, and immune cells were isolated by Ficoll density gradient centrifugation for single cell RNA sequencing analysis. Created in BioRender. Jin, W. (2026) https://BioRender.com/22ha1p. F UMAP of single cell RNA sequencing data colored by samples. Each panel shows identical cell population with one sample in color and all the others in gray. Regions containing T cells, myeloid cells, B cells, and epithelial cells/fibroblasts are indicated. G Representative B78 tumor photomicrographs for B cell marker CD20 at day 15 following 2 Gy 90Y-, 177Lu-, 225Ac-NM600 or 2 Gy EBRT + ICI or ICI alone; brown = positive immunolabeling. H Quantification of CD20+ cell clusters/tumor. Cell cluster: ≥5 cells. Scale bar = 200 μm. B–H Results of one experiment. B, C n = 10/treatment group. D–F 3 mice/treatment group pooled into one sample/treatment group for single cell RNA sequencing analysis. Numbers of cells analyzed provided in Supplementary Table 48. 90Y-NM600 + ICI, n = 6067; 177Lu-NM600 + ICI, n = 9808; 225Ac-NM600 + ICI, n = 6503; EBRT + ICI, n = 7045; ICI, n = 11,249. D–F n = 3 tumors/treatment group. G Representative image/treatment group from (H). H n = 4 tumors: 177Lu-NM600 + ICI; n = 3 tumors: 90Y-NM600 + ICI, 225Ac-NM600 + ICI, EBRT + ICI, ICI. Linear mixed models were used to compare tumor volumes over time between various treatment groups. Statistical testing of the pairwise contrasts was adjusted for multiple comparisons using Tukey’s method. Log-rank test was used to compare survival. One-way ANOVA with Tukey’s HSD post hoc test was used to compare CD20 IHC quantification between treatment groups. Error bars are SEM. E Created in BioRender. Jin, W. (2026) https://BioRender.com/22ha1p4.
