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. 2022 Oct 22;13:6292. doi: 10.1038/s41467-022-33991-6

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 8 — a Representative ultrasonographic images for orthotopic KPC tumor growth in vivo. Con, control; Gem, gemcitabine; ATG + Gem, Ate-Grab and gemcitabine cotreatment. b Tumor volumes compared across indicated treatment groups (Con, n = 6; Gem, n = 5; ATG + Gem, n = 7). ***P < 0.001; two-way ANOVA with Tukey’s multiple comparisons. c Representative images of KPC tumors. Ruler scale, 1 mm. d Tumor weights compared across indicated treatment groups (Con, n = 6; Gem, n = 5; ATG + Gem, n = 7). Data are presented as the mean ± SEM. *P < 0.05 (P = 0.030), ***P < 0.001, one-way ANOVA with Tukey’s multiple comparisons. e Representative SHG images of KPC tumors from each treatment group. Scale bars, 100 μm. f Average percentages of collagen⁺ area out of total area in tumors. Data from randomly selected fields of view were analyzed (Con, n = 48; Gem, n = 40; ATG + Gem, n = 56). Data are presented as the mean ± SEM. ***P < 0.001, one-way ANOVA with Tukey’s multiple comparisons. g Flow cytometry gating strategy to evaluate VEGF-related receptor expression in KPC tumor-infiltrated CAFs. Cells gated in red box were considered positive for the indicated receptors. Gating panel corresponds to FACS data in Fig. 8h. h Average percentages of NRP1-, VEGFR1-, or VEGFR2-expressing cells and triple negative cells for these receptors. Average percentages of i total CAFs (Gem vs ATG + Gem: P = 0.011) and j CD141⁺ MHC II⁻ CAFs (Con vs Gem: P = 0.006) in the KPC tumor microenvironment. Data from six mice from the control group, five mice from the gemcitabine group, and seven mice from the Ate-Grab+gemcitabine group were analyzed. Data are presented as the mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, one-way ANOVA with Tukey’s multiple comparisons. Average percentages of k CD3⁺ T cells (Gem vs ATG + Gem: P = 0.039), l CD4⁺ T cells, CD8⁺ T cells and Tregs in the KPC tumor microenvironment of each treatment group (Con, n = 6; Gem, n = 5; ATG + Gem, n = 6). Data are presented as the mean ± SEM. *P < 0.05 (Gem vs ATG + Gem in CD4⁺ T cells: P = 0.023, Con vs ATG + Gem in CD8⁺ T cells: P = 0.013), **P < 0.01 (Gem vs ATG + Gem in CD8⁺ T cells: P = 0.002), two-way ANOVA with Tukey’s multiple comparisons. Source data are provided as a Source Data file.