Fig. 3: Mdivi-1 improves the adoptive T cell therapy (ACT) in PDX tumor models by upregulating MHC-I. | Nature Communications

Fig. 3: Mdivi-1 improves the adoptive T cell therapy (ACT) in PDX tumor models by upregulating MHC-I.

From: Mitochondrial fission induces immunoescape in solid tumors through decreasing MHC-I surface expression

Fig. 3

A Scheme of ACT therapy through tumor-specific CTLs transferred into NOD/SCID mice transplanted with autologous HNSCC or NSCLC PDXs. B Tumor volume measurements were monitored weekly after ACT for five consecutive weeks (mean ± s.e.m; n = 3 per PDX group; p < 0.0001 for both HNSCC and NSCLC; **p < 0.001 by two-way ANOVA followed by Dunnett’s tests for multiple comparisons). C Weights of harvested HNSCC or NSCLC PDXs (mean ± s.e.m; n = 3 per PDX group; p = 0.0003, 0.0006 for HNSCC and 0.0006, 0.0011 for NSCLC; *p < 0.01, **p < 0.001 by one-way ANOVA followed by Dunnett’s tests for multiple comparisons). D Apoptosis of cancer cells as determined by EpCAM and TUNEL immunostaining (mean ± s.e.m; n = 9, 3 sections per PDX; p < 0.0001 for both HNSCC and NSCLC; **p < 0.001 by one-way ANOVA followed by Dunnett’s tests for multiple comparisons). E Flow cytometric analysis of MHC-I membrane expression in isolated HNSCC and NSCLC primary cancer cells. F indicates the fold change of MFI (mean fluorescence intensity) normalized to DMSO group (mean ± s.e.m; n = 3 per PDX group; p < 0.0001 or = 0.0792, 0.3609, 0.0002 for HNSCC and 0.0002, 0.0792, 0.3855, 0.0008 for NSCLC; **p < 0.001 compared with ACT accompanied by DMSO treatment or DMSO alone by one-way ANOVA followed by Dunnett’s tests for multiple comparisons). F Representative immunofluorescence images for EpCAM and CD8 of harvested PDXs (EpCAM: red; CD8: green). DAPI, nuclear staining. Scale bars, 25 μm. G Number of IFN-γ-producing CTLs as quantified by ELISpot (mean ± s.e.m; n = 3 per PDX group; p = 0.0002, 0.0004 for HNSCC and 0.0017, 0.0013 for NSCLC; *p < 0.01, **p < 0.001 by two-tailed t-test). H, I Evaluation of intracellular markers in association with cytotoxic function by flow cytometry (mean ± s.e.m; n = 3 per PDX group; p = 0.3405 or p < 0.0001 for perforin and 0.8773 or p < 0.0001 for granzyme B; **p < 0.001 compared with ACT accompanied by DMSO treatment by two-tailed t-test).

Back to article page