학술논문
Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy
Document Type
Original Paper
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. 25(4):644-658
Subject
Language
English
ISSN
1529-2908
1529-2916
1529-2916
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/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.
The spatial organization of cells in solid tumors is considered to be important for immune response and response to therapy. Here the authors use multiomics including spatial transcriptomics of human lung tumors prior to patients being treated and show among other things an association of stem-immunity hubs rich in stem-like CD8+ T cells with positive response to anti-PD-1 therapy.
The spatial organization of cells in solid tumors is considered to be important for immune response and response to therapy. Here the authors use multiomics including spatial transcriptomics of human lung tumors prior to patients being treated and show among other things an association of stem-immunity hubs rich in stem-like CD8