Fig. 1: LUAD is innervated by VSNs.

a, Representative immunofluorescence image showing TUBB3⁺ nerves (white) around tdTomato⁺ lung tumours (red) in KP; LSL-tdTomato mice (n = 3 mice). Scale bar, 100 μm. b, Experimental scheme, representative immunofluorescence images and quantification of BAF53b⁺ nerves (red) around zsGreen⁺ KP tumours (green, n = 6) or adjacent healthy alveolar regions (n = 5). P = 0.0409. Scale bar, 300 μm. c, Experimental scheme, representative immunofluorescence images, and quantification of VGLUT2⁺ nerves (red) around zsGreen⁺ KP tumours (green, n = 6) or adjacent healthy alveolar regions (n = 4). P = 0.0138. Scale bar, 200 μm. d, Experimental scheme, representative immunofluorescence images and quantification of GFP⁺ vagal sensory nerves (green) around tdTomato⁺ KP tumours (red, n = 11) or adjacent healthy alveolar regions (n = 8). P = 0.0410. Scale bar, 100 μm. White arrows denote tumour-innervating nerve fibres in b–d. e, Experimental scheme, representative immunofluorescence images and quantification of neurite outgrowth in cultured VSNs. The average length of TUBB3⁺ neurites per neuron was quantified under following treatments: control medium (control, n = 42), healthy LES (n = 49) or KP TES (n = 78, P < 0.0001 compared to control or LES). Each dot represents an individual VSN. Results shown are from one experiment, representative of three independent experiments. Scale bar, 200 μm. Cartoon was created in BioRender. Jin, C. (2026) https://BioRender.com/ujbfywi. f, Uniform manifold approximation and projection for dimension reduction (UMAP) plot showing all VSN clusters from scRNA-seq. Cells were isolated from the vagal nodose ganglia of healthy mice or littermates transplanted with KP lung tumours; VSNs were selected based on Phox2b expression. g, Violin plot showing Kcng1 expression across VSN clusters. h, UMAP plots displaying the cumulative fold change of differentially expressed genes (DEGs) in each VSN cluster (DEG cutoff: |log₂ fold change (FC) | >1, adjusted P < 0.05 by Wilcoxon rank-sum test, min. pct >0.1). i, Heat maps showing top DEGs in VSNs isolated from tumour-bearing versus healthy mice (adjusted P < 0.05 by Wilcoxon rank-sum test and |log₂FC | >1 in cluster 6). Data are expressed as mean ± s.e.m. Unpaired, two-tailed Student’s t-test (b–d); one-way ANOVA with Tukey’s multiple comparisons (e). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; NS, not significant (P ≥ 0.05).

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