Fig 2: Impact of savolitinib on immune infiltration, tumor growth, and splenocyte migration in immunocompetent and immunodeficient SCLC models(A) Immune infiltration analysis from KP1 model after treatment. Frequency of tumoral M-MDSC from KP1 tumors across treatments. Control (n = 4), cisplatin + isotype IgG (n = 2), cisplatin + savolitinib (n = 4), cisplatin + anti-PD-L1 (n = 4), cisplatin + anti-PD-L1 → savolitinib + anti-PD-L1 (n = 4), and cisplatin + anti-PD-L1 + savolitinib (n = 4).(B) Immune infiltration analysis from RPP631 model after treatment. Frequency of splenic CD11b+ cells from the spleens of RPP631-bearing mice across treatments. Chemo-immunotherapy (CI) (n = 10) and chemo-immunotherapy plus savolitinib (CI + SV) (n = 10).(C) Tumor growth curve of the KP1 model in NSG mice treated with cisplatin, savolitinib, and anti-PD-L1. Cisplatin + isotype IgG (n = 3), cisplatin + anti-PD-L1 (n = 3), and cisplatin + anti-PD-L1 + savolitinib (n = 4).(D) Tumor growth curve of the KP1 model treated with cisplatin, anti-PD-L1, and either savolitinib or anti-Gr1. Cisplatin + anti-PD-L1 (n = 5), cisplatin + anti-PD-L1 + anti-Gr1 (n = 5), and cisplatin + anti-PD-L1 + savolitinib (n = 6).(E) Migration of murine splenocytes after 4 h of exposure to an HGF gradient. The data plot shows the percentage of total seeded cells that migrated. Data are represented as the mean ± SD (n = 3). ∗∗p < 0.01; ∗∗∗∗p ≤ 0.0001.(F) Representative images of CD11b immunofluorescence staining in migrated KP1 splenocytes after 4 h of exposure to an HGF gradient (100 ng/mL). The control condition was RPMI 1640 medium without HGF. DAPI was used as a counterstain. From left to right: representative images of the DAPI (in blue) and CD11b (in green) channels and the merged composition. Scale bar: 100 μm.In (A) and (B), data are shown as means ± SD, with dots representing individual samples. ∗p < 0.05. In (C) and (D), data are shown as means ± SEM. No statistically significant differences were observed between groups (ns). See also Figures S5–S7.

Fig 3: Evolution of serum cytokine levels at different stages of SCLC and the association of HGF with EMT features(A) Boxplots representing sHGF levels (pg/mL) across different time points: baseline (TP1), response (TP2), and progression (TP3). TP1 (n = 81), TP2 (n = 53), and TP3 (n = 40).(B) Boxplots representing sHGF levels (pg/mL) across different SCLC subtypes. SCLC-A (n = 19), SCLC-N (n = 6), SCLC-P (n = 3), and SCLC-non-A/N/P (SCLC-I) (n = 8).(C) Correlation analysis between the H-score of EMT markers (E-cadherin and vimentin) and baseline sHGF levels. Pearson’s correlation analysis was performed for both markers.In (A) and (B), boxplot shows the median as a thick line, the box highlighting the first and third quartile with the whiskers plotted with the Tukey method.See also Figure S8.