Senescence-Induced Vascular Remodeling Creates Therapeutic Vulnerabilities in Pancreas Cancer

(Cell 181, 424–441.e1–e21; April 16, 2020) In the original article, we reported that senescence-inducing therapies can induce vascular remodeling that sensitizes pancreas cancers to chemo- and immunotherapies. We recently realized that we omitted some data that should have been included in the paper. This happened because we inadvertently failed to update four figure panels with some of the final study data that we collected, and for part of Figure S7, we inadvertently included data from S7D in S7F. We describe the errors below, and we are including updated versions of Figures 3F, 6A, S5B, and S7F. The errors do not alter the conclusions drawn from the figures. First, in Figure 3F, we omitted two values in the “T/P + Gem” group and one value in the “aVEGFR2” group that are now incorporated in the revised figure panel. We also identified a data point in the “aVEGFR2” group that was incorrect and has been updated. Second, in Figure 6A, we omitted one value for the “vehicle” group and one value for the “PD-1” group for both 2B4 and LAG3 expression, and one value for the “vehicle” group for CTLA-4 expression. We have updated Figure 6A to include these values, and we also acknowledge the correct n value (n = 5). Third, in Figure S5B, we omitted one value in the “vehicle” group and one value in the “T/P” group. We have updated Figure S5 to include these values, and we also acknowledge the correct n value (n = 8). Finally, in Figure S7F, we omitted one value in the “T/P+aPD-1 (Shp65)” group. Additionally, we mistakenly included three values to the “T/P+aPD-1 (ShRen)” group. This happened because we mistakenly included values in Figure S7F that came from the “T/P+aPD-1” group in Figure S7D. We have updated Figure S7F to include the appropriate values, and we also acknowledge the correct n value (n = 7). We sincerely apologize for any confusion these errors may have caused.Figure 6AT Cell Exhaustion Is Reversed by PD-1 Blockade that Triggers Anti-tumor ImmunityView Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure S5BTherapy-Induced Senescence Directly Promotes CD8+ T Cell Accumulation in PDACView Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure S7FSynergy between T/P Treatment and PD-1 Checkpoint Blockade Is Dependent on SASP-Mediated Vascular RemodelingView Large Image Figure ViewerDownload Hi-res image Download (PPT) Senescence-Induced Vascular Remodeling Creates Therapeutic Vulnerabilities in Pancreas CancerRuscetti et al.CellMarch 31, 2020In BriefIn mouse models of KRAS mutant pancreatic ductal adenocarcinoma, tumor cell senescence following MEK and CDK4/6 inhibition promotes vascular remodeling through induction of a pro-angiogenic senescence-associated secretory phenotype, leading to enhanced drug delivery and T cell infiltration that sensitizes these tumors to chemotherapy and immune checkpoint blockade. Full-Text PDF Open Archive