These tumor‐originated dynamics may dictate regional immune heterogeneity, with the reactive subtype (m‐ITH) exhibiting an inflamed TIME consistent with Tian's findings of the interplay between cancer cell ITH and the TME at the single‐cell level.[7b] Furthermore, ITH‐associated meta‐programs in malignant tumor cells showed a negative correlation with CD8+ T‐cells cytotoxicity and cell cycle meta‐programs,[18] suggesting a resistant microenvironment within highly heterogeneous tumors that impedes the recruitment of cytotoxic T‐cells. The gene discussed is CD8A; the disease is neoplasm.