Figure 7. Versikine promotes CD8⁺ responses and overcomes resistance to anti-PD1 inhibitors in vivo.

(A) Schematic of the experiment.

(B) Frequency of MHCI:SIINFEKL tetramer⁺CD8⁺ splenocytes in mice bearing LLC-EV versus LLC-Vkine tumors 5 days after challenge with a therapeutic dose of a STING agonist (DMXAA500). Data are presented as mean ± SEM.

(C) Correlation between in vitro versikine signature and CD8⁺ T cell scores across TCGA human lung cancers. Significance was measured using a linear model while accounting for total immune infiltration.

(D) DPEAAE staining in human lung cancers and associated CD8⁺ infiltration. 10× objective: scale bar, 50 μm.

(E) Distribution of DPEAAE stromal staining intensity across lung cancer prognostic subgroups (pauci-immune [poor prognosis] and immune-rich [favorable prognosis] at cutoff 3 CD8⁺ TILs/HPF). p < 0.001 by two-tailed Mann-Whitney test.

(F) Top: schematic of the experiment. Bottom: tumor growth rates and survival curves of LLC-EV and LLC-Vkine-bearing animals treated with 3 doses of anti-PD1 antibody or isotype control.

*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. In vitro experiments were performed in technical triplicates. In vivo cohort sizes are shown in individual panels. All experiments were reproduced independently at least twice.