Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy

Nat Immunol. 2024 Apr;25(4):644-658. doi: 10.1038/s41590-024-01792-2. Epub 2024 Mar 19.


The organization of immune cells in human tumors is not well understood. Immunogenic tumors harbor spatially localized multicellular 'immunity hubs' defined by expression of the T cell-attracting chemokines CXCL10/CXCL11 and abundant T cells. Here, we examined immunity hubs in human pre-immunotherapy lung cancer specimens and found an association with beneficial response to PD-1 blockade. Critically, we discovered the stem-immunity hub, a subtype of immunity hub strongly associated with favorable PD-1-blockade outcome. This hub is distinct from mature tertiary lymphoid structures and is enriched for stem-like TCF7+PD-1+CD8+ T cells, activated CCR7+LAMP3+ dendritic cells and CCL19+ fibroblasts as well as chemokines that organize these cells. Within the stem-immunity hub, we find preferential interactions between CXCL10+ macrophages and TCF7-CD8+ T cells as well as between mature regulatory dendritic cells and TCF7+CD4+ and regulatory T cells. These results provide a picture of the spatial organization of the human intratumoral immune response and its relevance to patient immunotherapy outcomes.

MeSH terms

  • CD8-Positive T-Lymphocytes
  • Chemokines / metabolism
  • Humans
  • Immunotherapy / methods
  • Lung Neoplasms*
  • Programmed Cell Death 1 Receptor
  • Tumor Microenvironment


  • Programmed Cell Death 1 Receptor
  • Chemokines