Extended Data Fig. 7: Genetic microglia depletion. | Nature Cancer

Extended Data Fig. 7: Genetic microglia depletion.

From: Targeting TGFβ-activated kinase-1 activation in microglia reduces CAR T immune effector cell-associated neurotoxicity syndrome

Extended Data Fig. 7: Genetic microglia depletion.

(a-f) Neurocognitive tests and flow cytometry analysis were performed on B-ALL-bearing littermate controls (WT) (mice, n = 5-7) or Cx3cr1CreER:Csf1rfl/fl mice (mice, n = 6-8) mice treated with CD19-CAR-T-cells. (g-l) Neurocognitive tests and flow cytometry analysis were performed on B-ALL-bearing littermate controls (WT) (mice, n = 6) or Csf1rΔFIRE/ΔFIRE mice (mice, n = 6) treated with CD19-CAR-T- cells. (m-r) Neurocognitive tests and flow cytometry were performed on B-ALL-bearing littermate controls (WT) (mice, n = 5-8) or HexBCreER: Csf1rfl/fl mice (mice, n = 5-8) treated with CD19-CAR- T-cells. In each model, the following were assessed: Neurocognitive function, Depletion efficacy of CD45loCD11b+cells, CNS-associated-macrophages (Perivascular, border associated and meningeal macrophages) quantification and tumor burden quantification by CD19+B220+CD45+ cells. (a, g, m) The scatter plot shows the percentage of open arm entries by WT littermate or Cx3cr1CreER:Csf1rfl/fl or Csf1rΔFIRE/ΔFIRE or HexBCreER: Csf1rfl/fl mice in an elevated plus maze test. (b, h, n) The scatter plot shows the time spent by WT littermate or Cx3cr1CreER:Csf1rfl/fl or Csf1rΔFIRE/ΔFIRE or HexBCreER: Csf1rfl/fl mice in exploring a novel object (exploration time/total time in %) in a novel object recognition test. (c, i, o) The scatter plot shows the grip strength of WT littermate or Cx3cr1CreER:Csf1rfl/fl or Csf1rΔFIRE/ΔFIRE or HexBCreER: Csf1rfl/fl mice normalized to body weight (N) in a grip strength test. (d, j, p) The scatter plot shows the quantification (absolute counts) of CD45loCD11b+ cells isolated from the CNS of the respective models as indicated. (e, k, q) The scatter plot shows the quantification (absolute counts) of CAMs cells of all CD11b+ cells isolated from the CNS. (f, l, r) The scatter plot shows the quantification (absolute counts) of CD19+B220+ of all CD45+ cells isolated from the spleen. Experiments were performed once (g-l, p-q), two independent times (a-f, m-o, r), and the results (mean ± s.e.m) were pooled. P-values were calculated using two-tailed unpaired student’s t-test (a,b,e (left),g, j, k(middle and right) (m-p, q (middle and right)) or two-tailed Mann-Whitney test (c, d, e(middle and right), f, h, j, k(left), l, q(left), r).

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