Journal: Molecular Therapy Oncology

Article Title: Oncolytic virotherapy mobilizes tumor-resident, granzyme B-producing bystander CD4 + T cells to inhibit systemic microbial infection

doi: 10.1016/j.omton.2026.201187

Figure Lengend Snippet: Dual protection against tumor and pathogen infection by the OV-BYTE strategy (A) Schematic of the experimental design for (B–D). C57BL/6 mice were infected with LCMV Armstrong and engrafted with MC38 cells on day 60 post-infection. On days 7–12 after tumor engraftment, recipients were daily administered PBS, NDV-WT, or NDV-GP daily via the intratumoral route. On day 15 after tumor engraftment, recipients were infected with either LM-GP 61-80 or IAV-GP 61-80 at an LD 50 dose. (B) Tumor growth curve of MC38 tumor-bearing mice intratumorally treated with PBS, NDV-WT, or NDV-GP as described in (A). (C and D) Survival curves of LM-GP 61-80 (C) and IAV-GP 61-80 (D) infection in MC38-engrafted mice treated with PBS, NDV-WT, or NDV-GP as described in (A). (E) Schematic of the experimental design for (F–H). C57BL/6 mice were infected with LCMV Armstrong and engrafted with B16F10 cells on day 60 post-infection. On days 7–12 after tumor engraftment, recipients were administered PBS, Ad5-WT, or Ad5-GP daily via the intratumoral route. On day 15 after tumor engraftment, recipients were infected with either LM-GP 61-80 or IAV-GP 61-80 at an LD 50 dose. (F) Tumor growth curve of B16F10 tumor-bearing mice intratumorally treated with PBS, Ad5-WT, or Ad5-GP as described in (E). (G and H) Survival curves of LM-GP 61-80 (G) and IAV-GP 61-80 (H) infection in B16F10-engrafted mice treated with PBS, Ad5-WT, or Ad5-GP as described in (E). (I) Schematic of the experimental design. Congenic CD45.1 + SM CD4 + T cells were adoptively transferred into naive C57BL/6 recipients (CD45.2 + ), which were then infected with LCMV Armstrong. On day 60 post-infection, these recipients were engrafted with MC38 cells. On days 7–12, these recipients were administered NDV-GP daily via the intratumoral route. Then, Ly108 hi CD39 lo and Ly108 lo CD39 hi SM CD4 + T cells in the spleens were isolated on day 15 post-tumor engraftment and subsequently transferred into MC38 tumor-bearing mice (no LCMV Armstrong infection) via intravenous injection, along with MC38 tumor-bearing mice receiving no cell transfer as control. One day later, all recipients were infected with LM-GP 61-80 at an LD 50 dose. (J) Survival curve of LM-GP 61-80 infection in groups described in (I). (K) Schematic of the experimental design. WT and Gzmb KO mice were infected with LCMV Armstrong. On day 60 post-infection, splenic LCMV Armstrong-activated CD4 + T MEM cells were harvested and adoptively transferred into another cohort of naive C57BL/6 mice. These recipients, along with control C57BL/6 mice with no CD4 + T MEM cell transfer, were then engrafted with MC38 tumor cells, intratumorally administrated NDV-WT or NDV-GP, and infected with LM-GP 61-80 at the indicated time points. (L) Survival curve of LM-GP 61-80 infection in groups described in (I). All data are representative of at least two independent experiments with at least eight mice per group. Not significant (ns), ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, and ∗∗∗∗ p < 0.0001 by two-way ANOVA (B, F) and log rank (Mantel-Cox) test (C, D, G, H, J, L). Center values and error bars (B, F) indicate mean and SEM.

Article Snippet: B16F10 (CRL-6475) cells were acquired from ATCC.

Techniques: Infection, Isolation, Injection, Control