a, Histological evaluation of KDM4A expression in tumor tissues. Left, representative images of IHC staining. Scale bar, 50 μm. Right, pathological scores (in a range of 1–4, averaged from 3 independent readings/animal) of KDM4A expressed in tumor tissues. b, Comparative evaluation of KDM4A expression in epithelial versus stromal cells isolated via LCM-based cell lineage-specific capture from the TME niche. Note, KDM4A induction was mainly observed in stroma upon MIT-mediated chemotherapeutic treatment. c, Histological evaluation of KDM4B expression in tumor tissues. At the end of therapeutic regimen, animals were sacrificed, with tissues processed for immunohistochemical (IHC) staining. Left, representative images of IHC staining. Scale bar, 50 μm. Right, pathological scores as described for a panel. d, Comparative evaluation of KDM4B transcript levels in epithelial versus stromal cells isolated via LCM-based cell lineage-specific capture from the TME niche. e, Histological evaluation of H3K9me3 and H3K36me3 in tumor tissues. At the end of therapeutic regimen, animals were sacrificed, with tissues processed for immunohistochemical (IHC) staining. Left, representative images of IHC staining. Scale bar, 100 μm. Green arrows, representative stromal cells. Right, statistical comparison of pathological scores (in a range of 1–4, averaged from 3 independent readings/animal) of H3K9me3 and H3K36me3 detected in tumor tissues. f, Heatmap depicting gene expression profile in stromal cells (PSC27) transplanted to experimental mice which experienced different therapeutic regimens. Cells were acquired through LCM after completion of treatments and histological process. Red stars, the SASP factors. Data are shown as mean ± SD and representative of 3 independent experiments. a (right panel), b, c (right panel), d, and e (right panel), P values were determined by two-sided unpaired t-test, and adjusted for multiple comparisons. b, d, Median, 25th and 75th percentiles, with Turkey whispers indicated in box-and-whisker plots and extending to values no further than 1.5 × IQR from either upper or lower hinge.