Pan-cancer profiling of tumor-infiltrating natural killer cells through transcriptional reference mapping.

Autor: Netskar H; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway., Pfefferle A; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden. aline.pfefferle@ki.se., Goodridge JP; Fate Therapeutics, San Diego, CA, USA., Sohlberg E; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden., Dufva O; Wellcome Sanger Institute, Wellcome Genome Clymphoid cells (ILCs)ampus, Hinxton, Cambridge, UK., Teichmann SA; Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.; Department of Medicine, University of Cambridge, Cambridge, UK., Brownlie D; Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Huddinge, Sweden., Michaëlsson J; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden., Marquardt N; Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Huddinge, Sweden., Clancy T; Oslo Cancer Cluster, NEC OncoImmunity AS, Oslo, Norway.; Department of Vaccine Informatics, Institute for Tropical Medicine, Nagasaki University, Nagasaki, Japan., Horowitz A; Department of Immunology & Immunotherapy, Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Malmberg KJ; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. k.j.malmberg@medisin.uio.no.; Precision Immunotherapy Alliance, University of Oslo, Oslo, Norway. k.j.malmberg@medisin.uio.no.; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden. k.j.malmberg@medisin.uio.no.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 Aug; Vol. 25 (8), pp. 1445-1459. Date of Electronic Publication: 2024 Jul 02.
DOI: 10.1038/s41590-024-01884-z
Abstrakt: The functional diversity of natural killer (NK) cell repertoires stems from differentiation, homeostatic, receptor-ligand interactions and adaptive-like responses to viral infections. In the present study, we generated a single-cell transcriptional reference map of healthy human blood- and tissue-derived NK cells, with temporal resolution and fate-specific expression of gene-regulatory networks defining NK cell differentiation. Transfer learning facilitated incorporation of tumor-infiltrating NK cell transcriptomes (39 datasets, 7 solid tumors, 427 patients) into the reference map to analyze tumor microenvironment (TME)-induced perturbations. Of the six functionally distinct NK cell states identified, a dysfunctional stressed CD56 bright state susceptible to TME-induced immunosuppression and a cytotoxic TME-resistant effector CD56 dim state were commonly enriched across tumor types, the ratio of which was predictive of patient outcome in malignant melanoma and osteosarcoma. This resource may inform the design of new NK cell therapies and can be extended through transfer learning to interrogate new datasets from experimental perturbations or disease conditions.
(© 2024. The Author(s).)
Databáze: MEDLINE
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