The study investigates the spatial organization of immune cells in human lung cancer and its association with the response to immunotherapy. The authors identified 'immunity hubs' in pre-immunotherapy lung cancer specimens, which are defined by the expression of chemokines that attract T cells and the presence of abundant T cells. They found that these immunity hubs are associated with a favorable response to PD-1 blockade immunotherapy. A specific subtype of immunity hub, called the 'stem-immunity hub,' was discovered, which is enriched for stem-like TCF7+PD-1+CD8+ T cells and is strongly associated with a better outcome. This hub is distinct from mature tertiary lymphoid structures and is characterized by the presence of activated dendritic cells, fibroblasts, and chemokines that organize these cells. The study also revealed preferential interactions between CXCL10+ macrophages and TCF7+CD8+ T cells, as well as between mature regulatory dendritic cells and Treg cells within the stem-immunity hub. These findings provide insights into the spatial organization of the intratumoral immune response and its relevance to patient immunotherapy outcomes.The study investigates the spatial organization of immune cells in human lung cancer and its association with the response to immunotherapy. The authors identified 'immunity hubs' in pre-immunotherapy lung cancer specimens, which are defined by the expression of chemokines that attract T cells and the presence of abundant T cells. They found that these immunity hubs are associated with a favorable response to PD-1 blockade immunotherapy. A specific subtype of immunity hub, called the 'stem-immunity hub,' was discovered, which is enriched for stem-like TCF7+PD-1+CD8+ T cells and is strongly associated with a better outcome. This hub is distinct from mature tertiary lymphoid structures and is characterized by the presence of activated dendritic cells, fibroblasts, and chemokines that organize these cells. The study also revealed preferential interactions between CXCL10+ macrophages and TCF7+CD8+ T cells, as well as between mature regulatory dendritic cells and Treg cells within the stem-immunity hub. These findings provide insights into the spatial organization of the intratumoral immune response and its relevance to patient immunotherapy outcomes.