Extended Data Fig. 8: Adoptively transferred CTLs with RGS1 knockdown reveals enhanced anti-tumor effects in breast cancer PDXs.
a, Representative ER−PR−HER2− PDX is shown in comparison with the original tumor samples, which was immunostained for ER, PR, HER2 and PD-L1 (n = 4 cases of PDX). Scale bar, 50 μm. b, Quantification of Fig. 6b (mean±s.e.m.; n = 4 cases of PDX; ****P < 0.0001). c,d, Representative immunofluorescence images for TUNEL/CD8 (c) or Ki-67/CD8 (d) co-staining in the harvested PDXs (n = 3 cases of PDX per group). White arrows indicate transferred CTLs. Scale bar, 50 μm. The bars at the bottom correspond to the percentages of apoptotic (c) or proliferative (d) CTLs (mean±s.e.m., n = 3 cases of PDX per group). *P = 0.0189 compared with shvec-transduced CTLs. e,f, PDX-infiltrating CTLs were isolated 7 days after T cell transfusion. e, Representative histograms of apoptosis of PDX-infiltrating CTLs, as determined by flow cytometry. Numerical values denote the percentages of cleaved caspase-3+ cells in gated CD8+ T cells (mean±s.e.m., n = 4 cases of PDX). **P = 0.0013 compared with shvec-transduced CTLs. f, The proliferation of transferred CD8+ T cells were assessed by flow cytometry for CFSE+ cells. Numbers denote the percentage of cells undergoing at least one cellular division (mean±s.e.m., n = 4 cases of PDX). g, PDX growth rates of SYMH133, SYMH137 and SYMH145 were determined by tumor volume (mean±s.d., n = 3 mice per group per PDX case). SYMH133: **P = 0.0064; SYMH145: *P = 0.0248 ((-) vs shvec-CTL/αPD-L1), 0.0108 (shRGS1-CTL/IgG vs shRGS1-CTL/αPD-L1); ****P < 0.0001. h, Quantification of Fig. 6f (mean±s.e.m., n = 4 cases of PDX). The exact P values are listed in the graph. ****P < 0.0001. P values were determined by two-tailed one-way ANOVA with Dunnett’s multiple comparison test (b-e) or two-tailed two-way ANOVA with Tukey’s multiple comparison tests (g, h).
