Illustration of the immune microenvironment modulation by T-DXd. Tumor biopsies at baseline and days 22-43 after cycle 1 of T-DXd were assessed by multiplex immunofluorescence (n = 31). No quantitative modulation of the immune microenvironment by T-DXd in the overall population (n = 31) was observed. There was a significant decrease in PD-L1 expression presumably due to the cytotoxic effect of T-DXd on tumor cells (CK + /PD-L1 + ) in patients with HER2-overexpressing mBC (n = 18, P = 0.002). Immune cells, represented by CD3 + /PD-L1 + or CD68 + /PD-L1 + , did not show a decrease during treatment in cohort 1 (n = 18, P = 0.42). No significant decrease of PD-L1 + tumor (P = 0.17) or immune cells (P = 0.65) was observed in patients with HER2-low and HER2-non-expressing mBC (n = 13) during treatment. Blue bullets and red bullets represent at-baseline and on-treatment samples, respectively. P values were calculated using the Wilcoxon matched-pairs signed-rank test. All statistical tests were two-sided.Mφ, macrophage; T reg , regulatory T cell.
