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

Autor: Chen JH; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA. jhchen@broadinstitute.org.; Department of Pathology, MGH, Boston, MA, USA. jhchen@broadinstitute.org.; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA. jhchen@broadinstitute.org.; Harvard Medical School, Boston, MA, USA. jhchen@broadinstitute.org., Nieman LT; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Spurrell M; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.; Department of Pathology, MGH, Boston, MA, USA.; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Jorgji V; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.; Department of Pathology, MGH, Boston, MA, USA.; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Elmelech L; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.; Department of Pathology, MGH, Boston, MA, USA.; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Richieri P; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA., Xu KH; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA., Madhu R; Harvard Medical School, Boston, MA, USA.; Brigham and Women's Hospital, Division of Genetics, Boston, MA, USA., Parikh M; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Zamora I; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Mehta A; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Harvard Medical School, Boston, MA, USA., Nabel CS; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Koch Institute for Integrative Cancer Research, Department of Biology, MIT, Cambridge, MA, USA., Freeman SS; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Harvard Medical School, Boston, MA, USA., Pirl JD; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., Lu C; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA., Meador CB; Harvard Medical School, Boston, MA, USA.; Department of Medicine, Division of Hematology/Oncology, MGH, HMS, Boston, MA, USA., Barth JL; Department of Pathology, MGH, Boston, MA, USA., Sakhi M; Center for Thoracic Cancers, MGH, Boston, MA, USA., Tang AL; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Sarkizova S; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Price C; Vizgen, Cambridge, MA, USA., Fernandez NF; Vizgen, Cambridge, MA, USA., Emanuel G; Vizgen, Cambridge, MA, USA., He J; Vizgen, Cambridge, MA, USA., Van Raay K; NanoString Technologies, Seattle, WA, USA., Reeves JW; NanoString Technologies, Seattle, WA, USA., Yizhak K; Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel., Hofree M; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.; Lautenberg Center for Immunology and Cancer Research, The Hebrew University of Jerusalem, Jerusalem, Israel., Shih A; Department of Pathology, MGH, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Sade-Feldman M; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Harvard Medical School, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Boland GM; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Harvard Medical School, Boston, MA, USA.; Department of Surgery, MGH, Boston, MA, USA., Pelka K; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Gladstone-UCSF Institute of Genomic Immunology, Gladstone Institutes, San Francisco, CA, USA., Aryee MJ; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.; Harvard Medical School, Boston, MA, USA.; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA., Mino-Kenudson M; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.; Department of Pathology, MGH, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Gainor JF; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA. jgainor@mgh.harvard.edu.; Harvard Medical School, Boston, MA, USA. jgainor@mgh.harvard.edu.; Center for Thoracic Cancers, MGH, Boston, MA, USA. jgainor@mgh.harvard.edu., Korsunsky I; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA. ikorsunsky@bwh.harvard.edu.; Harvard Medical School, Boston, MA, USA. ikorsunsky@bwh.harvard.edu.; Brigham and Women's Hospital, Division of Genetics, Boston, MA, USA. ikorsunsky@bwh.harvard.edu., Hacohen N; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA. nhacohen@mgh.harvard.edu.; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA. nhacohen@mgh.harvard.edu.; Harvard Medical School, Boston, MA, USA. nhacohen@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 Apr; Vol. 25 (4), pp. 644-658. Date of Electronic Publication: 2024 Mar 19.
DOI: 10.1038/s41590-024-01792-2
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 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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