Extended Data Fig. 10: Combination of HPCS or AT1-like cell state ablation with lung cancer therapies.

a-c, Data relating to Fig. 3l–m. a, Experimental design to test the effects of ablating Hopx⁺ AT1-like cells on tumour growth in subcutaneous KPfrt; Hopx^MACD/+ LUAD reporter allografts. Two weeks after transplantation, allograft-bearing mice were administered saline or DT (25 μg/kg, q.o.d.). Tumour volume measurement and AkaLuc bioluminescence signal detection were performed at the indicated time point. IVIS: in vivo imaging system. b, Hopx-AkaLuc bioluminescence signal intensity normalized to tumour volume in saline-treated (n = 10 tumours, 5 mice) vs. DT-treated (n = 8 tumours, 4 mice) allografts. Welch’s test. c, Tumour volume at indicated timepoints in allografts in mice administered either saline or DT. n = 8 tumours, 4 mice per group. Welch’s test. d-e, Data relating to Fig. 4a, b. G-Luc (d) and C-Luc (e) activity at indicated time points (normalized to day 1) in saline (n = 5 mice), cisplatin (n = 7 mice), or MRTX1133 (n = 8 mice) treated groups. Note: Fold change of C-Luc under MRTX1133 therapy: 4x (7 d), 3x (1 4 d), and 2x (21 d). Welch’s t-test. f-j, Data relating to Fig. 4c, d. f, Co-staining of PanCK (red), GFP (green, traced-HPCS) in KPfrt; Rosa26^mTmG/+; Slc4a11^MCD/+ LUAD tumours under indicated therapies for 3 weeks. Scalebar: 10 µm. g, Percentage of GFP⁺ cancer (panCK⁺) cells under saline (n = 34 tumours, 3 mice), cisplatin (n = 27 tumours, 3 mice), or MRTX1133 (n = 20 tumours, 3 mice) treatments. One-way ANOVA with Tukey’s multiple comparisons test. h, Percentage of HPCS-derived cells in the AT1-like cell state after 21 days of MRTX1133 therapy based on scRNA-seq analyses. n = 4 mice (saline), n = 6 mice (cisplatin), or n = 7 mice (MRTX1133). Kruskal-Wallis test. i, Co-staining of PanCK (red) and Cre (green, HPCS) in KPfrt; Rosa26^mTmG/+; Slc4a11^MCD/+ LUAD tumours under indicated therapies for 3 weeks. Scalebar: 10 µm. j, Percentage of Cre⁺ cancer cells under saline (n = 17 tumours, 3 mice), cisplatin (n = 21 tumours, 3 mice), or MRTX1133 (n = 13 tumours, 3 mice) therapy. One-way ANOVA with Tukey’s multiple comparisons test. k-l, Data relating to Fig. 4e, f. k, Experimental design to test the effect of ablating Hopx⁺ AT1-like LUAD cells by DT (25 μg/kg, q.o.d.) in the context of either saline control or cisplatin chemotherapy (1.5 mg/kg, every 3 days) in subcutaneous KPfrt; Hopx^MACD/+ LUAD reporter allografts. l, Volume of subcutaneous KPfrt; Hopx^MACD/+ LUAD allografts subjected to saline control, DT, or cisplatin, alone, or in combination, as in (k). Saline, DT, and cisplatin: n = 8 tumours, 4 mice. Combination: n = 10 tumours, 5 mice. Two-way ANOVA with Tukey’s multiple comparisons test. Error bars are SEM. The diagrams in a and k were created using BioRender. Tammela, T. (2025) https://BioRender.com/0lgfrw5.

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