Publication
Fibroblastic reticular cells generate protective intratumoral T cell environments in lung cancer.
Journal Paper/Review - Nov 19, 2024
Onder Lucas, Papadopoulou Chrysa, Lütge Almut, Cheng Hung-Wei, Lütge Mechthild, Pérez Shibayama Christian Ivan, Gil Cruz Cristina, De Martin Angelina, Kurz Lisa, Cadosch Nadine, Pikor Natalia, Rodriguez Regulo, Born Diana, Jochum Wolfram, Leskow Pawel, Dutly André Emanuel, Robinson Mark D, Ludewig Burkhard
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PubMed
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Issn Electronic
Brief description/objective
Stringent control of T cell activity in the tumor microenvironment is essential for the generation of protective antitumor immunity. However, the identity, differentiation, and functions of the cells that create critical fibroblastic niches promoting tumor-infiltrating T cells remain elusive. Here, we show that CCL19-expressing fibroblastic reticular cells (FRCs) generate interconnected T cell environments (TEs) in human non-small cell lung cancer, including tertiary lymphoid structures and T cell tracks. Analysis of the FRC-T cell interactome in TEs indicated molecular networks regulating niche-specific differentiation of CCL19-expressing fibroblasts and T cell activation pathways. Single-cell transcriptomics and cell fate-mapping analyses in mice confirmed that FRCs in TEs originate from mural and adventitial progenitors. Ablation of intratumoral FRC precursors decreased antitumor T cell activity, resulting in reduced tumor control during coronavirus vector-based immunotherapy. In summary, specialized FRC niches in the tumor microenvironment govern the quality and extent of antitumor T cell immunity.