Fig. 4: Leptomeningeal IFNγ supports cDC maturation.
From: Interferon-γ orchestrates leptomeningeal anti-tumour response
a, In vivo radiance of LLC LeptoM cells delivered intracisternally into Zbtb46-DTR (recipient C57BL/6-Tyrc-2) bone marrow chimeras, treated with DTx and measured 2 weeks after cancer cell injection (Methods and Extended Data Fig. 11). b, In vivo radiance of LLC LeptoM cells delivered intracisternally into Clec9acre and Clec9acreRosa26lsl-DTR mice treated with DTx, 2 weeks after injection. c, In vivo radiance of LLC LeptoM cells delivered intracisternally into Zbtb46-DTR (recipient C57BL/6-Tyrc-2) bone marrow chimeras overexpressing eGFP or Ifng into the leptomeninges, treated with DTx, 2 weeks after injection. d, t-Distributed stochastic neighbour embedding (t-SNE) of mouse leptomeningeal DC types from vehicle- (veh.) and LLC LeptoM-injected mice 2 weeks after inoculation, analysed using 10x CITE-seq (Methods and Extended Data Fig. 12). n = 7,566 cells pooled from 4 conditions, n = 6 animals per group. e, Surface protein and Ccr7 gene expression in DCs from the experiment in d. f, Gene expression trends associated with cDC2, CCR7+ identity and IFNγ signalling along the diffusion pseudotime axis, as determined using Palantir35. g, In vivo radiance of LLC LeptoM cells delivered intracisternally into mice with WT cDCs and mice with ΔIfngr1 cDCs, 2 weeks after injection. h, The proportion of mature leptomeningeal CCR7+ (CD11c+MHC-II+) DCs in LLC LeptoM-bearing Ifngr1-proficient and Ifngr1-deficient mice. i, T cell-derived IFNγ governs maturation of leptomeningeal cDC2 subset into mature, migratory CCR7+ DCs. j, UMAP of identity (left) and cell cycle phase prediction (right) in LLC LeptoM cancer cells expressing cytokeratin and CD63. n = 3,161 and n = 557 cells from mice overexpressing eGFP and Ifng in the leptomeninges, respectively; n = 6 mice per group. k, Quantification of the experiment in e (Methods and Extended Data Fig. 13i–k). l, Representative image of cleaved-caspase-3-stained (Cl. CASP3) E0771 LeptoM in mice overexpressing eGFP or Ifng in the leptomeninges. Scale bars, 50 μm; br., brain parenchyma. See also Extended Data Fig. 13l–n.
