Fig. 4

Evaluation of tumor microenvironment after IT1208 administration. a and b. Representative images of biopsy specimens stained using mFIHC pre (a) and post (b) IT1208 treatment in Case 10. Upper photographs show H&E staining with low (left) and high (right) magnification (scale bars: 500 or 100 μm, respectively). Activation of T cells was determined by visualizing nuclear Ki67 (pink) expression in each subset. CD4⁺ or CD8⁺ T cells were detected by visualizing CD3 (blue) and CD4 (green) double-positive or CD3 (blue) and CD8 (red) double-positive cells, respectively. Tumor (T) and stroma (S) were determined as CK-positive (orange) and -negative areas, respectively. White arrowheads (▽) in lower right images indicate CD3⁺CD8⁺Ki67^high cells. c and d. Changes in CD3⁺CD8⁺ or CD3⁺CD4⁺ T cells (c), and the Ki67^high population (d) after IT1208 treatment. The density of each T-cell subset was evaluated (Appendix Table A2), and the ratio of changes between pre and post IT1208 treatment in each patient is shown. e. Heat map of the changes in gene expression in the tumor biopsies following IT1208 treatment. Columns represent fold changes in expression of each gene or the relative value of gene expression, while rows represent case number. The Z-scaled fold changes by column are shown