Fig. 3: The non-malignant TME mediates antitumor efficacy of PVSRIPO in mice.

a, b B16^WT or B16^CD155 cells were treated in vitro with mRIPO (MOI 10). Viability (a) was measured by WST1 assay, values were normalized to %mean “0” time point, and immunoblot analysis (b) of cell lysates for CD155, STAT1, and viral protein (2C, 2BC). c, d PEC from WT (PEC^WT) or CD155-tg (PEC^CD155) mice were treated with mock, mRIPO (MOI 10), or UV-inactivated mRIPO (MOI 10 pre-inactivation titer) in vitro (48 h). Supernatant cytokines (c) were measured and immunoblot analysis (d) was performed as in (b). a–d n = 4 experiments, (a, c) mean −/+ SEM are shown, symbols (* and #) denote significant Tukey’s post-hoc test (p < 0.05, two-tailed) compared to “0” time point (a, *, p < 0.0001 for both) or all other groups (c, #). e Wt or CD155-tg B16 cells were implanted into wt or CD155-tg mice to test (left to right): no infection (wt cells & hosts, n = 6 mock, 8 mRIPO), malignant cell only infection (B16-CD155-tg, wt hosts, n = 6 mock, 8 mRIPO), TME only infection (wt cells, CD155-tg hosts, n = 7 mock, 6 mRIPO), or TME + malignant cell infection (both CD155-tg, n = 9 mock, 8 mRIPO). Mice were treated intratumor with PBS or mRIPO (1 × 10⁷ pfu) on day 0; PD-L1 blocking antibody was injected i.p. in all groups as shown. Mean tumor volume (mm3) + SEM are shown at each test interval; p-values are from two-way ANOVA (two-tailed); a representative series from two experiments is shown.