Fig. 7: Oncolytic adenovirus expressing ApoA1 subverts TAM fragility and potentiates antitumor responses in GBMs.

a Construction of recombinant oncolytic adenoviruses (AdV^Ctrl and AdV^APOA1). b Western blot detection of ApoA1 protein expression in AdV^APOA1-infected 293T cells. Culture supernatant and cell lysate were collected for identification of ApoA1 protein levels. n = 2 independent experiments. c In vivo replication and expression of AdV^APOA1. n = 3 mice per group. (d) Representative immunofluorescence images of in vivo infection, replication and expression of AdV^APOA1. The images are representative of 2 tumors per group. e–g Experimental setup (e), IVIS real-time monitoring (f), and representative H&E staining of tumor growth in vivo following intratumoral injection of oncolytic adenovirus in an immune-competent murine GL261^CAR-luc model. n = 6 mice per group. Kaplan–Meier survival curves and body weights of intracranial GL261^CAR-bearing C57BL/6 J mice (h) and intracranial G422^CAR-bearing KM mice (i) that received treatment as indicated. GL261, n = 7 mice per group. G422, n = 6 mice per group. Experimental setup (j), tumor growth monitoring (k), and Kaplan–Meier survival curves and body weights (l) of an immune-reconstructive human GBM model treated with the indicated oncolytic adenoviruses. n = 7 mice per group. Heatmap of differentially expressed genes (m), lipid metabolism genes (n), and phagocytosis genes (o) in oncolytic virus-treated tumor tissues. A total of 733 DEGs were identified. n = 3 biological samples per group. p Quantification of ex vivo phagocytosis in TAMs. GL261^CAR-REP cells were infected with saline, AdV^Ctrl (MOI = 10) or AdV^APOA1 (MOI = 10) for 24 h. n = 3 biological samples per group. Quantification of the expression of the “don’t eat me” receptor (q) and MHC-II (r) on TAMs. Siglec-10/PD-1, n = 9 mice per group. MHC-II, n = 7 mice per group. s The ratio of tumor-infiltrating lymphoid cells to tumor cells. n = 7 mice per group. Statistical significance was determined using the unpaired t test (Two-tailed) in c, d, p, the Mann–Whitney test (Two-tailed) in f, k, q, r, s, the log-rank test in h, i, l. All data are the mean ± SD. Source data are provided in the Source Data file.