Fig. 4: CAF senescence correlates with reduced T cell presence in mouse and human PDACs. | Nature Communications

Fig. 4: CAF senescence correlates with reduced T cell presence in mouse and human PDACs.

From: Senescent cancer-associated fibroblasts in pancreatic adenocarcinoma restrict CD8+ T cell activation and limit responsiveness to immunotherapy in mice

Fig. 4

a Co-staining of 6422c1 KPC xenograft tumors for p16 together with either Pdpn, marking CAFs, CD31 marking endothelial cells, CD45 marking immune cells, and Mac2, marking macrophages. Images show examples of double-positive cells of each type. b Percentages of cells expressing the indicated lineage markers out of p16+ stromal cells in the 6422c1 KPC xenografts, as shown in panel a. Mean of n = 2–4 tumors as indicated ± SEM. c Sections of tumors that developed from different KPC PDAC lines that were injected into mouse pancreata, stained for p16 (top), or co-stained for p16, CD3, marking T cells, and YFP, marking the cancer cells (bottom). Tumors on left, which developed from the 6555c3 line, show low levels of p16+ CAFs and high T cell numbers, whereas tumors on right, which developed from the 6422c1 and 6499c3 lines, show high levels of p16+ CAFs and low T cell numbers. d Correlation between percentage of p16+ cells out of CAFs, and CD3+ T cell numbers per mm2, in individual tumors grown from distinct KPC lines, quantified by image analysis. R value indicates Pearson correlation with calculated P value, with line indicating linear regression. n = 9 tumors. e Correlation between percentage of Pdpn+ CAFs out of stromal area, and CD3+ T cell numbers per mm2 tumor, in same tumors as in (d). n = 9 tumors. f Images of regions in human PDACs co-stained for p16, CD3, and CK18 marking tumor cells (top) or for CD8 and GZMB (bottom, same regions in sequential sections). Left images show region with low p16+ CAF content and high CD3+ , CD8+ and GZMB+ CD8+ cell numbers; right images show region with high p16+ CAF content and low T cell numbers. Quantifications are provided in (g). g Correlation between percentages of p16+ cells out of VIM+ CAFs in 57 tumor regions in 11 human PDACs, and T cell numbers in same regions, scored by image analysis. y axes in graphs indicate numbers CD3+ , CD8+ or GZMB+ CD8+ T cells per mm2 as indicated; bottom right graph shows percentage of GZMB+ out of CD8+ T cells in y axis. R values indicate Spearman correlation with calculated P value. Scale bars = 20 μm.

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