Serial Low Doses of Sorafenib Enhance Therapeutic Efficacy of Adoptive T Cell Therapy in a Murine Model by Improving Tumor Microenvironment
Figure 5
Serial low doses of sorafenib augment recruitment and activation of transferred CD8+ T cells, and exhibit better tumor responses of ACT.
(A) The experimental design in vivo. (B) Bioluminescent imaging was used to monitor the activation of CD8+ T cells from day 0 post ACT. Transferred CD8+ T cells survived longer in tumor lesions in 2T+sora group compared with that of CD8+ T cells alone group. (C) Quantification of BLI signals from tumors. No significant difference was found between 2T+ sora and 5T groups. Though no significant difference was found between 2T+ sora and 2T groups, about two folds higher average radiance was shown in 2T+ sora group as compared with that of 2T group. (D) Tumor growth was tracked by caliper measurement. Significant tumor shrinkage was observed in 5T and 2T+ sora groups, and no significant difference was found between these two groups. Shrinkage of tumors initiated from day 3 after ACT. Notably, day 3 was the time point with peak BLI signals. The experiments were repeated five times, and one of the representative was shown here. (*as compared with that of the control group, * p<0.05, ** p<0.01, **** p<0.0001; # as compared with that of the sorafenib group, #p<0.05, ##p<0.01; †as compared with that of the 2T group, †p<0.05)