Fig. 9: Synergizing effects of PFM037 and immunotherapy in controlling lung and melanoma tumor growth and analysis of myeloid cells infiltrating human tumors. | Cell Death & Disease

Fig. 9: Synergizing effects of PFM037 and immunotherapy in controlling lung and melanoma tumor growth and analysis of myeloid cells infiltrating human tumors.

From: Harnessing the reverse cholesterol transport pathway to favor differentiation of monocyte-derived APCs and antitumor responses

Fig. 9

A LLC tumor growth in mice treated with PFM037, anti-PD-1 mAb, the combination therapy, or vehicle plus ctrl mAb (n = 5 mice/group). ***P < 0.001; ****P < 0.0001; ns, not significant (Student’s t-test). B Overall survival of LLC-bearing mice treated with PFM037, anti-PD-1 mAb, the combination therapy, or vehicle plus ctrl mAb (n = 6 mice/group). Statistical comparison was performed by log-rank test (vehicle vs anti-PD1, P = 0.0051; vehicle vs PFM037, P = 0.0051; vehicle vs PFM037 + anti-PD1, P = 0.0009). C, D Tumor volume (C) and overall survival (D) of NOD-SCID mice challenged with LLC-OVA and treated with PFM037 and/or adoptive cell therapy with in vitro activated OT-I T cells (n = 5 mice/group). For tumor volume **P = 0.0018; ****P = 0.0001 (Student’s t-test). For overall survival statistical comparison was performed by log-rank test (PFM037 vs OT-I, P = 0.0027; PFM037 vs PFM037 + OT-I, P < 0.014; OT-I vs PFM037 + OT-I, not significant). E B16F1-OVA tumor weight following the treatment with vehicle, PFM037, in vitro activated OT-I alone, or in combination with PFM037 (n = 5 mice/group). **P < 0.01; ***P < 0.001 (Anova). F Average expression heatmap (normalized-UMI) of reverse cholesterol transport (RCT)/cholesterol synthesis genes in NSCLC immune-infiltrating cell populations [43]. Insert displays t-SNE plots of all cells profiled, color-coded according to the expression of ABCA1 and SCD transcripts in the same populations. G Average expression heatmap (normalized-UMI) of LXR/cholesterol synthesis genes in tumor-associated monocyte/macrophage and DC subsets of myeloid cells [43]. Insert displays t-SNE plots of myeloid cells profiled, color-coded according to the expression of ABCA1 and SCD transcripts in the same populations. (H) Dot plots of LXR/cholesterol synthesis genes in melanoma-infiltrating monocytes and DCs profiled, divided in Responder and Non-Responder patient-cells [44]. Each dot is colored according to the expression value and the size is related to the percentage of cells expressing the gene in the population of interest.

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