학술논문
Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy
Document Type
Article
Author
Chen, Jonathan H.; Nieman, Linda T.; Spurrell, Maxwell; Jorgji, Vjola; Elmelech, Liad; Richieri, Peter; Xu, Katherine H.; Madhu, Roopa; Parikh, Milan; Zamora, Izabella; Mehta, Arnav; Nabel, Christopher S.; Freeman, Samuel S.; Pirl, Joshua D.; Lu, Chenyue; Meador, Catherine B.; Barth, Jaimie L.; Sakhi, Mustafa; Tang, Alexander L.; Sarkizova, Siranush; Price, Colles; Fernandez, Nicolas F.; Emanuel, George; He, Jiang; Van Raay, Katrina; Reeves, Jason W.; Yizhak, Keren; Hofree, Matan; Shih, Angela; Sade-Feldman, Moshe; Boland, Genevieve M.; Pelka, Karin; Aryee, Martin J.; Mino-Kenudson, Mari; Gainor, Justin F.; Korsunsky, Ilya; Hacohen, Nir
Source
Nature Immunology; April 2024, Vol. 25 Issue: 4 p644-658, 15p
Subject
Language
ISSN
15292908; 15292916
Abstract
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/CXCL11and 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.