Print Email Facebook Twitter Distinct spatiotemporal dynamics of CD8+ T cell-derived cytokines in the tumor microenvironment Title Distinct spatiotemporal dynamics of CD8+ T cell-derived cytokines in the tumor microenvironment Author Hoekstra, Mirjam E. (Netherlands Cancer Institute) Slagter, Maarten (Netherlands Cancer Institute) Urbanus, Jos (Netherlands Cancer Institute) Toebes, Mireille (Netherlands Cancer Institute) Slingerland, Nadine (Netherlands Cancer Institute) de Rink, Iris (Netherlands Cancer Institute) Kluin, Roelof J.C. (Netherlands Cancer Institute) Nieuwland, Marja (Netherlands Cancer Institute) Wessels, L.F.A. (TU Delft Pattern Recognition and Bioinformatics; Netherlands Cancer Institute) Date 2024 Abstract Cells in the tumor microenvironment (TME) influence each other through secretion and sensing of soluble mediators, such as cytokines and chemokines. While signaling of interferon γ (IFNγ) and tumor necrosis factor α (TNFα) is integral to anti-tumor immune responses, our understanding of the spatiotemporal behavior of these cytokines is limited. Here, we describe a single cell transcriptome-based approach to infer which signal(s) an individual cell has received. We demonstrate that, contrary to expectations, CD8+ T cell-derived IFNγ is the dominant modifier of the TME relative to TNFα. Furthermore, we demonstrate that cell pools that show abundant IFNγ sensing are characterized by decreased expression of transforming growth factor β (TGFβ)-induced genes, consistent with IFNγ-mediated TME remodeling. Collectively, these data provide evidence that CD8+ T cell-secreted cytokines should be categorized into local and global tissue modifiers, and describe a broadly applicable approach to dissect cytokine and chemokine modulation of the TME. Subject cytokineIFN-gammasingle cell RNA-seqT cellTNF-alphatumor microenvironment To reference this document use: http://resolver.tudelft.nl/uuid:00b696c3-aa93-46b6-b1a7-ea27ee13c13e DOI https://doi.org/10.1016/j.ccell.2023.12.010 ISSN 1535-6108 Source Cancer Cell, 42 (1), 157-167.e9 Part of collection Institutional Repository Document type journal article Rights © 2024 Mirjam E. Hoekstra, Maarten Slagter, Jos Urbanus, Mireille Toebes, Nadine Slingerland, Iris de Rink, Roelof J.C. Kluin, Marja Nieuwland, L.F.A. Wessels, More Authors Files PDF 1_s2.0_S1535610823004385_main.pdf 11.31 MB Close viewer /islandora/object/uuid:00b696c3-aa93-46b6-b1a7-ea27ee13c13e/datastream/OBJ/view