Fig. 2: Neoadjuvant chemotherapy impacts the TME.
From: Persister cell phenotypes contribute to poor patient outcomes after neoadjuvant chemotherapy in PDAC
a, Top, significantly enriched immune cell types. Middle, significantly expressed immunosuppressive genes. Bottom, significantly expressed immunostimulatory genes. Significance was determined by two-sided Wilcoxon rank-sum test adjusted for multiple testing (P ≤ 0.05); TH1, type 1 helper T cell. b, Immune cell types that exhibit significant enrichment in chemo-naive (n = 32) and post-CTX (n = 33) samples. The heat map represents median immune cell enrichment, and the bar chart represents significance of enrichment as –log10 (Wilcoxon rank-sum test two-sided P value adjusted for multiple testing (Padj)); HSC, hematopoeitc stem cell; aDC, activated dendritic cell; TCM, central memory T cell; GMP, granulocyte–monocyte progenitor; Treg, regulatory T cell; CMP, common myeloid progenitor. c, Bar charts showing significant enrichment of specific stromal signatures in post-CTX samples; myCAFs, myofibroblast-like CAFs; iCAFs, inflammatory CAFs. The significance is provided as –log10 (Wilcoxon rank-sum test two-sided P value adjusted for multiple testing). The dotted line represents –log10 (Padj ≤ 0.05). d, Volcano plots showing the enrichment of immunomodulatory and myofibroblastic cell signature genes in samples treated preoperatively with GEM or mFFX. Genes significantly enriched (log2 (fold change) of >1 and –log10 (Padj) of >2) in post-CTX mFFX samples are shown. Padj represent the significance of a two-sided Wald test adjusted for multiple testing; FC, fold change. e, Kaplan–Meier survival analysis for high (greater than median) and low (less than median) macrophage M2 enrichment values in post-CTX (GEM and mFFX) and mFFX PDAC-HD samples. Participant numbers for each group are provided under ‘Numbers at risk’. A log-rank (two-sided) P value of ≤0.05 is considered significant. f, Immune cell types that exhibit significant enrichment in mFFX post-CTX samples (n = 23) relative to GEM post-treated samples (n = 10). The heat map represents median immune cell enrichment, and the bar chart represents the significance of enrichment as –log10 (Wilcoxon rank-sum test two-sided P value adjusted for multiple testing). g, Immunostimulatory genes that are significantly and differentially expressed between post-CTX GEM (n = 10) and mFFX (n = 23) samples. The bar chart provides the significance of enrichment as –log10 (Wilcoxon rank-sum test two-sided P value adjusted for multiple testing). Correlation heat map showing correlations between immunomodulatory factors in post-CTX samples. Pearson’s correlations are shown in the plot. Significance was determined by two-sided Pearson’s correlation test. P values were not adjusted for multiple testing. All correlations shown are significant.
