Extended Data Fig. 2: Ablation of vagal NPY2R/TRPV1 neurons inhibits LUAD growth.

a-b, Experimental setup, representative IF images, and quantification showing the depletion efficiency of Npy2r⁺ or P2ry1⁺ VSNs in Npy2r-ires-cre; lsl-DTR mice (n = 4 PBS, n = 6 DT) or P2ry1-ires-cre; lsl-DTR mice (n = 4 PBS, n = 8 DT) that were injected with PBS or DT in the VNG. Percentages of DTR+ neurons in total TUBB3⁺ cells in the VNG were calculated; p < 0.0001 for both (a) and (b). c, UMAP plots showing Trpv1, Npy2r and P2ry1 expression in lung-innervating VSNs (K1-K3, L1 and A3) from the single-cell RNA-seq dataset described in Zhao et al. 2022¹⁵. d, Quantification of anterogradely labelled Trpv1⁺ or Npy2r⁺ vagal sensory fibers around tumour regions or adjacent healthy alveolar regions (Trpv1-cre: n = 5 tumour regions, n = 7 healthy regions, p = 0.0205; Npy2r-ires-cre: n = 6 tumour regions, n = 6 healthy regions, p = 0.0122). e, Experimental setup, representative IF images, and quantification showing the depletion efficiency of Trpv1⁺ VSNs in Trpv1-cre; lsl-DTR mice that were injected with PBS or DT in the VNG (n = 4 PBS, n = 4 DT, p < 0.0001). f, Representative images and quantification of Npy2r (cyan) and Trpv1 (red) by RNA-scope in the VNG from Trpv1-cre, lsl-DTR mice vagally injected with PBS (n = 4) or DT (n = 4). g, Experimental scheme and tumour burden quantification indicated by total lung weight in lsl-DTR (n = 9) or Trpv1-cre;lsl-DTR (n = 8) mice both receiving identical vagal DT treatment. p = 0.0024. h, Flow-cytometric analysis of tumour-bearing lungs from lsl-DTR (n = 7) or Trpv1-cre;lsl-DTR (n = 5) mice both receiving identical vagal DT treatment. Left, percentage of alveolar macrophages (AMs) expressing ARG1, p = 0.0233; middle, percentage of CD8⁺ T cells co-expressing IFN-γ and TNF-α, p = 0.0449; right, percentage of CD4⁺ T cells expressing IFN-γ, p = 0.0213. Data are expressed as mean ± s.e.m. Unpaired, two-tailed Student’s T-test (a,b,d,e,g,h) was performed.

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