Fig. 5: cDC cytokines support NK cell activity to control cancer cell growth.
From: Interferon-γ orchestrates leptomeningeal anti-tumour response
a, t-SNE projection of leptomeningeal NK cells from vehicle- and LLC LeptoM-injected mice 2 weeks after inoculation, analysed using 10x CITE-seq. Total of n = 2,247 cells from 4 conditions, n = 6 mice per group (Methods). b, Cell-state-enriched NK surface protein expression from the experiment in a. N, naive; A, activated; P, proliferative; S, senescent-like. c, NK cell cycle prediction from the experiment in a (Methods). d, Selected CCR7+ DC ligand and NK cell receptor expression from the experiment in a, projected onto t-SNE plots (Methods). e, The relative abundance of CSF IL-12, IL-15 and IL-18 from patients without and with LM, as determined using targeted proteomics. Statistical analysis was performed using multiple t-tests. f, Human NK surface protein expression, as determined using single-cell transcriptomics. g, NK cell survival in the CSF of patients without and with LM. Two independent experiments (Methods). h, NK cell survival in human LM− CSF with or without recombinant mouse IL-12 and IL-15. Four independent experiments. Statistical analysis was performed using paired t-tests (Methods). i, In vivo radiance of LLC LeptoM cells delivered intracisternally into C57BL/6-Tyrc-2 mice overexpressing eGFP or Ifng in the leptomeninges treated with isotype or asialo-GM1 antibodies, 2 weeks after injection. j, In vivo radiance of LLC LeptoM cells delivered intracisternally into C57BL/6 Ifngr1−/− and Ifngr1+/+ mice treated with isotype or asialo-GM1 antibodies, 2 weeks after injection. k, In vivo radiance of LLC LeptoM cells delivered intracisternally into mice with WT NK cells and mice with ΔIfngr1 NK cells, 2 weeks after injection. l, NK products in the CSF of patients without and with LM, as determined using bead arrays. Statistical analysis was performed using multiple t-tests. m, In the leptomeninges, T cells produce IFNγ, supporting maturation of conventional DC2 cells into migratory CCR7+ DCs. These DCs produce IL-12 and IL-15 to support the survival and proliferation of NK cells, which control the expansion of metastatic cells.
