| Autor: |
Chen JH, Nieman LT, Spurrell M, Jorgji V, Richieri P, Xu KH, Madhu R, Parikh M, Zamora I, Mehta A, Nabel CS, Freeman SS, Pirl JD, Lu C, Meador CB, Barth JL, Sakhi M, Tang AL, Sarkizova S, Price C, Fernandez NF, Emanuel G, He J, Raay KV, Reeves JW, Yizhak K, Hofree M, Shih A, Sade-Feldman M, Boland GM, Pelka K, Aryee M, Korsunsky I, Mino-Kenudson M, Gainor JF, Hacohen N |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2023 Apr 06. Date of Electronic Publication: 2023 Apr 06. |
| DOI: |
10.1101/2023.04.04.535379 |
| Abstrakt: |
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 that they were associated with beneficial responses to PD-1-blockade. Immunity hubs were enriched for many interferon-stimulated genes, T cells in multiple differentiation states, and CXCL9/10/11 + macrophages that preferentially interact with CD8 T cells. Critically, we discovered the stem-immunity hub, a subtype of immunity hub strongly associated with favorable PD-1-blockade outcomes, distinct from mature tertiary lymphoid structures, and enriched for stem-like TCF7+PD-1+ CD8 T cells and activated CCR7 + LAMP3 + dendritic cells, as well as chemokines that organize these cells. These results elucidate the spatial organization of the human intratumoral immune response and its relevance to patient immunotherapy outcomes. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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