Fig. 5: Necroptosis promotes the establishment of immune-suppressive inflammation, metastasis and features of stemness.

a RP (n = 3) and RPC (n = 3) mice were sacrificed 5 days after Ad-Cre inhalation. Representative images of histological analysis and indicated stainings of lungs are shown. Non-inhaled controls received intratracheal PBS. Scale bars represent 10 mm for TUNEL stainings and 100 μm for all other. b qPCR analysis for the indicated genes from whole lungs 5 days post Ad-Cre inhalation are shown. RP (n = 3), RPC (n = 3), RP-MlklAA/AA (n = 4) and RPC-MlklAA/AA (n = 5). Data are presented as mean values ± SEM of the biological replicates c 12 weeks post Ad-Cre inhalation, immune cells were isolated from whole lungs of RP (n = 4), RPC (n = 6), RP-MlklAA/AA (n = 5) and RPC-MlklAA/AA (n = 5) mice followed by FACS analysis. Proportions of M2 macrophages (CD11b+CD206+) and Tregs (CD4+CD25+foxp3+) within single/live immune cells are shown. d % of mice with or without metastasis 30 weeks post Ad-Cre inhalation. RP (n = 26), RPC (n = 7), RP-MlklAA/AA (n = 6) and RPC-MlklAA/AA (n = 6). e % of mice with more or less than 3 macroscopic lung tumor nodules 30 weeks post Ad-Cre inhalation, RP (n = 24), RPC (n = 8), RP-MlklAA/AA (n = 5) and RPC-MlklAA/AA (n = 7). f qPCR analysis comparing gene expression between RP (n = 5), RPC (n = 9), RP-MlklAA/AA (n = 6) and RPC-MlklAA/AA (n = 6) endpoint tumors. Relative expression compared to the housekeeping gene actin is shown. g proposed sequence of events in the RPC mouse. Created in BioRender. Stroh, J. (2025) https://BioRender.com/k47q488. b Two-tailed unpaired t tests. c One-way ANOVA (uncorrected Fisher´s LSD). d, e Fischer´s exact test. Source Data are provided as a Source Data file.