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Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy.
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.
Afiliação
  • Chen JH; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA. jhchen@broadinstitute.org.
  • Nieman LT; Department of Pathology, MGH, Boston, MA, USA. jhchen@broadinstitute.org.
  • Spurrell M; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA. jhchen@broadinstitute.org.
  • Jorgji V; Harvard Medical School, Boston, MA, USA. jhchen@broadinstitute.org.
  • Elmelech L; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
  • Richieri P; Harvard Medical School, Boston, MA, USA.
  • Xu KH; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
  • Madhu R; Department of Pathology, MGH, Boston, MA, USA.
  • Parikh M; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Zamora I; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
  • Mehta A; Department of Pathology, MGH, Boston, MA, USA.
  • Nabel CS; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Freeman SS; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
  • Pirl JD; Department of Pathology, MGH, Boston, MA, USA.
  • Lu C; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Meador CB; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
  • Barth JL; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
  • Sakhi M; Harvard Medical School, Boston, MA, USA.
  • Tang AL; Brigham and Women's Hospital, Division of Genetics, Boston, MA, USA.
  • Sarkizova S; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
  • Price C; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Fernandez NF; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Emanuel G; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
  • He J; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Van Raay K; Harvard Medical School, Boston, MA, USA.
  • Reeves JW; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
  • Yizhak K; Harvard Medical School, Boston, MA, USA.
  • Hofree M; Koch Institute for Integrative Cancer Research, Department of Biology, MIT, Cambridge, MA, USA.
  • Shih A; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Sade-Feldman M; Harvard Medical School, Boston, MA, USA.
  • Boland GM; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Pelka K; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  • Aryee MJ; Massachusetts General Hospital (MGH) Cancer Center, Harvard Medical School (HMS), Boston, MA, USA.
  • Mino-Kenudson M; Harvard Medical School, Boston, MA, USA.
  • Gainor JF; Department of Medicine, Division of Hematology/Oncology, MGH, HMS, Boston, MA, USA.
  • Korsunsky I; Department of Pathology, MGH, Boston, MA, USA.
  • Hacohen N; Center for Thoracic Cancers, MGH, Boston, MA, USA.
Nat Immunol ; 25(4): 644-658, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38503922
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pulmonares Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pulmonares Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article