FIGURE 4.

PD-1 antibody therapy in combination with intrapleural VV-IL-2 provides comparable efficacy and TIL infiltration. A, MPD mice were treated with systemic anti–PD-1 (n = 9), intrapleural VV-IL-2 (n = 20), or combination therapy (n = 9); (2 pooled experiments). Kaplan–Meier survival estimate (with 95% confidence interval) demonstrate that combination therapy or VV-IL-2 alone improved survival compared with anti–PD-1 alone. B, Bioluminescent imaging at days 7 and 14 showed evidence of tumor regression at day 14 in the combination and VV-IL-2 cohort compared with anti–PD-1 alone. C, Combination therapy or VV-IL2 alone decreased tumor mass compared with anti–PD-1 only treatment. D, Flow cytometry analysis of the immune infiltrates of the tumor for CD3⁺, CD4⁺, CD8⁺, and CD8⁺ PD-1⁺ expression (percent of all live cells) demonstrate no difference between combination therapy versus VV-IL-2 alone. However, enhanced adaptive immunity through increased CD3⁺, CD4⁺, and CD8⁺ immune cell infiltration was evident after local VV-IL-2 or combination treatment (compared with systemic anti–PD-1 only). Splenocytes demonstrated decreased CD4⁺ and elevated CD8⁺ PD-1 expressing T cells after combination therapy compared with systemic anti–PD-1 alone. P values are reported (*P < .05, **P < .01, ***P < .001).