Fig. 5: The vagal sensory-to-sympathetic axis suppresses anti-tumour immunity through β₂ adrenergic signalling in alveolar macrophages.

a, Experimental setup (left), representative H&E-stained lung sections (middle) and tumour quantification (right) from Trpv1-cre; LSL-DTR mice that received VNG PBS injection (G1, n = 12), VNG DT injection (G2, n = 13) or VNG DT injection plus daily aerosolized salbutamol treatment (G3, n = 12). Lung tumour burden was assessed by tumour/tissue area (G1 versus G2: P = 0.0133; G2 versus G3: P = 0.0131) and total lung mass (G1 versus G2: P = 0.0101; G2 versus G3: P = 0.0005). Scale bars, 1 mm. b, Representative H&E-stained lung sections and tumour quantification from wild-type (WT, n = 7) and Adrb2^−/− mice (n = 7). Lung tumour burden was assessed as tumour/tissue area (P = 0.0398) and total lung mass (P < 0.0001). Scale bars, 1 mm. c,d, Quantification of ARG1⁺ alveolar macrophages (c), IFNγ⁺TNF⁺ CD8 T cells and TNF⁺ CD4 T cells (d) in tumour-bearing lungs from wild-type (n = 7) and Adrb2^−/− mice (n = 5–6). c, P = 0.0004. d, CD8: P = 0.0037; CD4: P = 0.0213. e, Experimental setup (left), representative H&E-stained lung sections (middle) and tumour quantification (right) from irradiated Trpv1-cre; LSL-DTR mice that were reconstituted with wild-type or Adrb2^−/− bone marrow (BM) and injected with PBS or DT in the VNG. WT BM: n = 8 PBS (G1), n = 8 DT (G2); Adrb2^−/− BM: n = 10 PBS (G3), n = 10 DT (G4); pooled from 2 independent experiments. Scale bars, 1 mm. 5.1× and 1.3× denote fold change of tumour/tissue area between indicated groups. f,g, Quantification of ARG1⁺ alveolar macrophages (f), IFNγ⁺TNF⁺ CD8 T cells and TNF⁺ CD4 T cells (g) in tumour-bearing lungs from bone marrow chimeric mice described in e. h,i, Arg1 expression in cultured alveolar macrophages measured by quantitative PCR with reverse transcription (RT–qPCR). h, Wild-type alveolar macrophages were untreated or treated with 10 μM noradrenaline (NA) (n = 4 per group, P < 0.0001). i, Wild-type or Adrb2^−/− alveolar macrophages were pretreated with 10 μM noradrenaline and then either left untreated (n = 4 per group, P = 0.0001) or treated with TES (n = 4 per group, P = 0.0073). Data are presented as fold change relative to untreated wild-type alveolar macrophages (h,i). Results shown are representative of at least two independent experiments. Data are expressed as mean ± s.e.m. Unpaired, two-tailed Student’s t-test (b–d,h) or one-way ANOVA with Tukey’s multiple comparisons (a,e–g,i). Exact P values for e–g are provided in the Methods.

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