Fig. 2: Host IFNγ signalling suppresses leptomeningeal cancer growth.
From: Interferon-γ orchestrates leptomeningeal anti-tumour response
a, Representative images of haematoxylin-stained cytospins from vehicle-injected (top) and E0771 LeptoM-injected (bottom) mice. n = 3 per group. Scale bars, 50 μm. See also Extended Data Fig. 2. b, UMAP analysis of leptomeningeal cellular material from vehicle- and LLC LeptoM-injected mice 2 weeks after inoculation, after single-cell proteogenomic profiling using 10x CITE-seq. n = 7,528 (vehicle injected) and n = 19,534 (LLC LeptoM-injected) cells, n = 6 mice per group. See also Supplementary Figs. 2 and 3. c, Embedding density plots from LM− and LM+ mice, projecting the relative cell type abundance per condition onto the UMAP. d, Cytometry bead array quantification of CSF IFNγ from naive or LeptoM-bearing mice. e, Representative leptomeningeal tissue sections were stained with haematoxylin and eosin (H&E). Scale bars, 100 μm. The box plot shows the brain surface area covered with pigmented B16 LeptoM cells delivered intracisternally into C57BL/6 Ifng-proficient and Ifng-deficient mice, 2 weeks after injection. f, In vivo radiance of LLC LeptoM cells delivered intracisternally into mice with WT T cells and mice with ΔIfng T cells, quantified 2 weeks after injection. g, In vivo radiance of LLC LeptoM cells delivered intracisternally into mice with WT NK cells and mice with ΔIfng NK cells, quantified 2 weeks after injection. h, Representative leptomeningeal tissues were stained with H&E. The box plot shows the brain surface area covered with pigmented B16 LeptoM cells delivered intracisternally into C57BL/6 Ifngr1−/− and Ifngr1+/+ mice, 2 weeks after injection. The basilar meninges of these animals is shown. Scale bars, 100 μm (left) and 5 mm (right). i, Survival of mice after control LeptoM cells (sglacz, n = 10) and two Ifngr2-deficient B16 LeptoM clones (sg1, n = 10 and sg2, n = 9) were delivered intracisternally into C57BL/6 mice. Median overall survival: mOS sglacz (18 days), sg1 (15 days), sg2 (18 days). j, Schematic showing that the leptomeningeal T cells are the dominant generator of IFNγ-mediated cancer cell elimination.
