Fig. 6: Inactivation of DHODH in cancer cells enhance the anti-tumor activity of PD-1 blockade in mouse models. | Nature Communications

Fig. 6: Inactivation of DHODH in cancer cells enhance the anti-tumor activity of PD-1 blockade in mouse models.

From: DHODH modulates immune evasion of cancer cells via CDP-Choline dependent regulation of phospholipid metabolism and ferroptosis

Fig. 6: Inactivation of DHODH in cancer cells enhance the anti-tumor activity of PD-1 blockade in mouse models.The alternative text for this image may have been generated using AI.

A Effects of BRQ combined with anti-PD-1 treatment on the growth of D4M-UV3 tumors in C57BL/6 mice. (n = 7 mice for each group). B Effects of anti-PD-1 and IgG control treatments on the growth of DHODH-expressing versus DHODH KO D4M tumors in C57BL/6 mice. (n = 13 mice for DHODH KO anti-PD-1 group, n = 11 mice for other groups). C Analysis of tumor-infiltrating T cells revealed a significant increase in CD8+ T cells in DHODH-deficient D4M tumors (n = 11 mice each group). D Analysis of tumor-infiltrating CD4+ T cells revealed a similar representation in DHODH-expressing and DHODH KO D4M tumors (n = 11 mice each group). E Infiltrating CD8+ T cells isolated from DHODH KO tumors exhibited increased INFγ expression, compared to those from DHODH WT tumors (n = 9 mice for each group) (F) Immunofluorescence analysis of tumors from various treatment groups from (B) with 4-HNE antibody. G Quantification of 4-HNE staining (n = 5 each condition). H Cytotoxic T Lymphocyte (CTL) signature score analysis of RNASeq data obtained from various groups of D4M tumors (n = 6 for each group). I Spatial expression pattern of DHODH in tumor cells and T cell in human melanoma metastasis specimens. J Average distances of T cell to tumor cells with high or low DHODH levels as presented in panel I. Data are presented with median values shown in boxplots, where the lower and upper hinges correspond to 25th and 75th percentiles (H) or 10th and 90th percentiles (J) of the data. The lower and upper whisker range from minimum to maximum. K Schematic diagram of the model on how DHODH regulates tumor cell immune evasion. The cell icons were created in BioRender62. For panels A, B, the adjusted p values were calculated using a two-sided Tukey’s multiple comparisons test. For panels C–E, H and J, p values were calculated by unpaired two-tailed Student’s t-tests. For panel G, p values were calculated using original one-way ANOVA test. Data are represented as mean ± SEM. Source data are provided as a Source Data file.

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