T-cell numbers may matter less than their neighborhood. ICI-responsive melanoma was not simply richer in activated lymphocytes. The distinguishing feature was spatial organization: clonally expanded CD8⁺ tumor-resident T cells, CD4⁺ resident T cells and DC3 dendritic cells assembled into local immune triads found only in responding tumors. TCF1⁺ progenitor-like resident CD8⁺ cells were also enriched, suggesting these niches may continuously replenish cytotoxic effectors rather than merely host terminally activated cells. The counterpoint is equally interesting. Resistant tumors still carried strong IFN-γ programs, but alongside exhaustion and an immunosuppressive macrophage state. So an “inflamed” tumor is not necessarily an effective one. The relevant variable may be whether inflammation is organized into a functional local circuit connecting dendritic cells, helper T cells and renewable cytotoxic T cells. The study is associative—32 lymph-node metastases included only six ICI responders—and cannot establish that these triads cause response. But it argues that spatial immune architecture may be a more informative biomarker than T-cell abundance or IFN-γ signaling alone. #immunotherapy #T_cell #Australia nature.com/articles/s41467-0…