Fig. 8: Intratumoral administration of oncolytic AdVAPOA1 elicits systemic antitumor immune responses.

Quantification of intratumoral infiltrating immune cell subsets (a), PD-L1 expression in tumor cells (b), CD44/IFN-γ/Gzm-B expression in CD8⁺ T cell (c), and PD-1/LAG-3/TIGIT immune checkpoint expression in CD8⁺ T cells (d). Immune cells, n = 9 mice per group. PD-L1, n = 9 mice per group. CD44/IFN-γ/Gzm-B, n = 10 mice per group. PD-1/LAG-3/TIGIT, n = 10 mice per group. e Quantification of PD-1⁺LAG-3⁺ exhausted tumor-infiltrating CD8⁺ T cells. Saline, n = 9 mice. Virus, n = 11 mice. f Network diagram of GO enrichment analysis of differentially expressed genes in AdV^Ctrl- and AdV^APOA1-treated tumor bulks. Data are related to the experimental data (Fig. 7m). Experimental setup (g) and tumor growth curves (h) of the subcutaneous contralateral GBM model. n = 9 mice per group. Quantification of tumor-infiltrating CD8⁺ T cells (i) and viral replication (j) in the subcutaneous bilateral model. CD8⁺ T cell, n = 8 mice per group. Virus replication, n = 5 samples per group. k Kaplan–Meier survival curves of AdV^APOA1-treated GL261^CAR-bearing mice with or without depletion of immune cells. Intracranial GL261^CAR-bearing C57BL/6J mice were injected i.p. with isotype IgG, anti-CD8, or anti-CSF1R antibodies on days 2, 7, 12 and 17 after tumor inoculation. Mice received i.t. injection of saline or 1 × 10⁸ PFU AdV^APOA1 on day 7 and day 12 after tumor inoculation. Survival was monitored every day. n = 6 mice per group. l Schematic diagram of macrophage plasticity in a cholesterol-rich microenvironment. Cholesterol accumulation leads to phagocytic fragility in TAMs by inhibiting mitochondrial translation via 7-ketocholesterol. By manipulating cholesterol efflux through ApoA1, we were able to improve TAM function and enhance TAM-T-cell-mediated antitumor responses. Additionally, intratumoral administration of ApoA1-armed oncolytic adenovirus was found to remodel the immunometabolic microenvironment and promote antitumor immune responses. Statistical significance was determined using the Mann–Whitney test (two-tailed) in a–e, i, j, or the log-rank test in k. All data are the mean ± SD. Source data are provided in the Source Data file.