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. 2021 Oct 28;9(11):e003036. doi: 10.1136/jitc-2021-003036

Figure 4.

Figure 4

Therapeutic effects of PD-L1-targeted NIR-PIT could extend to distant non-NIR light irradiated tumors, inducing abscopal effects. (A) PD-L1-targeted NIR-PIT regimen is shown. (B) Mice with bilateral flank tumors were either injected with control F(ab′)2–IR700 or PD-L1-F(ab’)2-IR700, followed by NIR light irradiation of only the right tumor. One day after PD-L1-F(ab′)2-IR700 administration, the tumor on the right was irradiated with NIR light. (C) In vivo BLI of bilateral flank tumor model is demonstrated. In vivo BLI showed changes in bioluminescence signals in both tumors in response to PD-L1-targeted NIR-PIT on the right tumor. However, NIR light irradiation with control F(ab′)2–IR700 induced no decrease in either tumor. Before NIR-PIT, tumors were approximately the same size and exhibited similar bioluminescence. (D) Tumor volume ratio (as defined before NIR-PIT=1). PD-L1-targeted NIR-PIT introduced on day 0 led to significant tumor-volume reductions in the treated right and untreated left side (n=4–6 in each group) (PD-L1:R vs Cont:R and L at day 1:*p<0.001; PD-L1:L vs Cont:R and L at day 1:*p<0.01; PD-L1:R vs Cont:R and L at day 2:*p<0.01; PD-L1:L vs Cont:R and L at day 2:*p<0.05;PD-L1:R vs Cont:R and L at day 3:*p<0.01; PD-L1:L vs Cont:R and L at day 3:*p<0.05;PD-L1:R vs Cont:R and L at day 6:*p<0.001; PD-L1:L vs Cont:R and L at day 6:*p<0.01, PD-L1:R vs Cont:R and L at day 8:*p<0.01; PD-L1:L vs Cont:R and L at day 8:*p<0.05, PD-L1:R vs Cont:R and L at day 10:*p<0.01; Tukey’s test with two-way repeated measures ANOVA). (E) PD-L1-targeted NIR-PIT led to prolonged survival in bilateral tumor-bearing mice (n=9 in each group) (*p<0.0001, log-rank test). (F) CD8 T and NK cells collected from non-irradiated left dorsal tumors in mice receiving PD-L1-targeted NIR-PIT on the right dorsal tumors were analyzed for their expression of activation markers at 6 hours after the treatment (n=3; *p<0.05, **p<0.01, Student’s t-test). ANOVA, analysis of variance; NIR-PIT, near-infrared photoimmunotherapy; NK, natural killer; PD-L1, programmed death-ligand 1.