Figure 4. Juxtatumoral exclusion of CD8⁺ T-cells in KPC mice is reversed upon stromal collapse engineered by targeting stellate cells with ATRA.

KPC mice with fully developed tumours (day 60-200) were enrolled into a pre-clinical trial where they were either given vehicle (n=4) or ATRA (n=6). ATRA, selectively targets and restores stellate cells quiescence.¹¹ Proportion of CD8⁺ (A,B), CD4⁺ (C), CD45R⁺ (D), F4/80⁺ (E) and CD11b⁺ (F) cells in the panstromal and juxtatumoral compartments were measured as shown in Supplementary Figure 12. All data are presented as box (median with interquartile ranges (25^th and 75^th)) and whisker (5^th and 95^th centiles) plots. The juxtatumoral exclusion of CD8⁺ (cytotoxic T-cells) and CD45R⁺ (B-cells) cells was demonstrated in vehicle-treated mice. There was a significant increase in the CD8⁺ T-cell infiltrate (A,B) into the juxtatumoral compartment upon treatment of mice with ATRA which was not seen for CD4⁺ (helper T-cells), CD45R⁺ (B-cells), F4/80⁺ (macrophages) or CD11b⁺ (MDSC) cells.

Scale bar: 100μm

Mann-Whitney U-test, all p-values are two-tailed. ** p= 0.001 to 0.01; n.s.= not significant