Pembrolizumab(Keytruda) induced resistant model in B-hPD-1/hPD-L1 mice. (A) Pembrolizumab induced resistant model by multiple rounds of hPD-1 antibody retreatment on MC38-bearing humanized B-hPD-1/hPD-L1 mice. (B) The anti-tumor drug efficacy on MC38 cells before (TGl: 82.2%) and after induction validated the successful establishment of the hPD-1 antibody-resistant model B-Pembrolizumab-R-MC38 cells.

TILs profiling in hPD-1 antibody resistant animal models. Tumor tissues from indicated groups after treatment were collected and analyzed by flow cytometry at the end of the study. The specific immune cell subsets were quantified as in (A) mCD45+ cells in live cells. (B) CD3+ cells in mCD45+ cells.  (C) CD8+ cells in CD3+ cells. (D) mCD274+ (mPD-L1) in Mcd45- cells. (E) MHCII in mCD45- cells. (F) MDSC in mCD45+ cells.   (G) CD4+ cells in CD3+ cells. (H) MHCI in MDSC.  Data shown as mean ± SEM and analyzed using one-way ANOVA followed by Tukey's test comparing each group.   ( *p<0.05, **p<0.01, ***p<0.001)