Fig. 7: Repression of Tsp-1 by PRSS2 creates and immunosuppressive TME.

A Immunofluorescence staining of CD3 (green) and FoxP3 (red) in tumors formed by Pan02 (n = 4) and Pan02shPRSS2 (n = 3) cells in WT C57Bl6/J mice and Tsp1^−/− C57Bl6/J mice (scale bar = 1 mm). B Plot of the percentage of CD3 + /FoxP3 + T cells out of total CD3 + T cells in tumors formed by Pan02 (n = 4) and Pan02shPRSS2 (n = 3) cells in WT C57Bl6/J mice and thbs1^−/− C57Bl6/J mice (P value calculated via two-sided Mann–Whitney U test). C Immunofluorescence staining of CD3 (green), CD4 (red), and CD8 (white) in tumors formed by Pan02 (n = 4) and Pan02shPRSS2 (n = 3) cells in WT C57Bl6/J mice and Tsp1^−/− C57Bl6/J mice (scale bar = 1 mm). D Plot of percentage of CD3 + /CD8 + T cells out of total CD3 + T cells in tumors formed by Pan02 (n = 4) and Pan02shPRSS2 (n = 3) cells in WT C57Bl6/J mice and thbs1^−/− C57Bl6/J mice (P value calculated via two-sided Mann–Whitney U test). E Plot of ratio of CD3 + /CD8 + T cells to CD3 + /FoxP3 + T cells in tumors formed by (n = 4) and Pan02shPRSS2 (n = 3) cells in WT C57Bl6/J mice and thbs1^−/− C57Bl6/J mice (WT/WT minimum = 0.099; maximum = 0.58; median = 0.37; percentile = 25–75; P value calculated via two-sided Mann–Whitney U test). F Representative pictures of immunohistochemistry of CD8 + and FoxP3 + T cells in prostate tumors (n = 458 patients) with high or weak levels of PRSS2 (scale bar = 50 μm). G Kaplan–Meier curves of: upper left: correlation of high PRSS2 and low CD8 levels with survival after radical prostatectomy. Upper right: correlation of high PRSS2 and high FoxP3 levels with survival after radical prostatectomy; and lower left: correlation of low PRSS2 and high CD8 levels with survival after developing castration resistance; and lower right: correlation of high PRSS2 and high FoxP3 levels with survival after developing castration resistance (P values calculated via two-sided Mann–Whitney U test). H Schematic diagram of PRSS2 regulation of tumor immune microenvironment.