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.

人类肿瘤中免疫细胞的组织尚不清楚。免疫原性肿瘤具有空间定位的多细胞“免疫中心”，由 T 细胞吸引趋化因子CXCL10/CXCL11的表达和丰富的 T 细胞定义。在这里，我们检查了人类免疫治疗前肺癌标本中的免疫中枢，发现与 PD-1 阻断的有益反应存在关联。至关重要的是，我们发现了干免疫中枢，这是免疫中枢的一种亚型，与有利的 PD-1 阻断结果密切相关。该中心不同于成熟的三级淋巴结构，富含干细胞样 TCF7 ⁺ PD-1 ⁺ CD8 ⁺ T 细胞、活化的CCR7 ⁺ LAMP3 ⁺树突状细胞和CCL19 ⁺成纤维细胞以及组织这些细胞的趋化因子。在干免疫中心内，我们发现CXCL10 ⁺巨噬细胞与TCF7 ⁺ CD8 ⁺ T 细胞之间以及成熟调节性树突细胞与TCF7 ⁺ CD4 ⁺和调节性 T 细胞之间存在优先相互作用。这些结果提供了人类肿瘤内免疫反应的空间组织及其与患者免疫治疗结果的相关性的图片。