Fig. 4: Lymphoneogenic ILC2s migrate to tumours through a microbiota- and PDAC-modulated gut–blood circuit.

a, Parabiotic mice with PDACs in recipient pancreata. Donors were treated with vehicle or rIL-33. Quantification (top) and gating (bottom) of donor-derived ILC2s in recipient blood and PDAC. b, KikGR PDAC mice were treated daily with rIL-33 for 6 days. On day 6, the gut or peritoneum was photoconverted. Experimental schematic (left) and density of gut-derived (RFP⁺) ILC2s in pancreatic PDACs (right). c, Gut Il33 mRNA was analysed by digital droplet PCR in sham-treated and PDAC mice. d, Gut Il33 mRNA (left), blood KLRG1⁺ ILC2s (middle) and the intratumoural TLS density (right) in rIL-33-treated PDAC mice treated with or without antibiotics (Abx). e, The intratumoural KLRG1⁺ ILC2 frequency, number and TLS density in skin (s.c.) PDACs in vehicle-treated and rIL-33-treated mice with s.c. alone (single PDAC) or s.c. and pancreatic PDACs (dual PDAC). f, Parabiotic mice with s.c. PDACs in recipients with or without pancreatic PDACs in donors. Donors were treated with vehicle or rIL-33. The donor-derived ILC2 frequency in recipient s.c. PDACs (bottom) is shown. g, Parabiotic mice with s.c. PDACs in recipients and pancreatic PDACs in donors. Donors were treated with rIL-33; donor and recipients were treated with antibiotics. The donor-derived ILC2 number and frequency in recipient s.c. PDACs and gut (bottom) are shown. Data were collected at 2 weeks (a, e (left), f and g), as shown in the experimental schema (b), 4 weeks (c and d) and 5 weeks (e (right)) after tumour implantation, pooled from ≥2 independent experiments with n ≥ 3 mice per group with consistent results. n values represent the number of individual tumours or organs from individual mice analysed separately. The horizontal bars show the median. P values were calculated using two-tailed Mann–Whitney U-test (a, c, d, e (right) and g), one-way ANOVA with Kruskal–Wallis multiple-comparison test (b), two-way ANOVA with Kruskal–Wallis test (d, middle) and two-way ANOVA with Sidak’s multiple-comparison test (e (left) and f). Scale bar, 20 μm (e).

Source Data