Fig. 4: HER3-DXd intratumoral distribution and interaction with TCs.

a, Dynamics of HER3-DXd⁺ cells over the different time points. b, Mean tumor shrinkage in patients with ≥5% of HER3-DXd⁺ cells and those with <5% HER3-DXd⁺ cells at C1D3 (Student’s t-test, P = 0.0146). The 5% cut-off was chosen according to the minimal detectable percentage of HER3-DXd⁺ cells. The boxes represent the IQR and the whiskers extend to the minimum and maximum values within each group. c, Left: image of a tumor with HER3-DXd staining ≥5% of TCs at C1D3: intact-DXd⁺ cells 21% of the PANK⁺ cells. Right: image of a tumor with HER3-DXd staining <5% of TCs at C1D3: intact-DXd⁺ cells 0.25% of the PANK⁺ cells. PANK⁺ cells are shown in red and Intact-DXd⁺ cells in blue; similar staining patterns were observed across all analyzed samples (n = 20). d,e, Volcano plot of differentially expressed genes in paired on-T and BL tumor samples in responders (d) and nonresponders (e). The P values shown are from two-sided tests and were adjusted for multiple comparisons using the Benjamini–Hochberg method. f, Volcano plot of differentially expressed genes in on-treatment samples of HER3-DXd⁺ (≥5% TCs, n = 5) and HER3-DXd⁻ (<5% TCs, n = 7) tumors. The P values shown are from two-sided tests and were adjusted for multiple comparisons using the Benjamini–Hochberg method.