Fig. 4: Carboplatin increases CAR T cell accumulation and activation in PDX-287R.

a, b Number of CD3⁺ T cells per mm², based on immunohistochemistry (a), and representative immunohistochemistry images of CD3⁺ T cells (b) in PDX-287R grafts 5–6 weeks post-treatment with no T cell control (n = 8 grafts), carboplatin (n = 5 grafts), docetaxel (DTX; n = 6 grafts), nivolumab (n = 7 grafts), ev-T cells (n = 8 grafts), CAR T cells (n = 7 grafts), nivolumab (nivo) + CAR T cells (n = 6 grafts), carboplatin (carbo) + CAR T cells (n = 9 grafts), and DTX + CAR T cells (n = 3 grafts). c, d Number of CD8⁺ effector T cells per mm², based on immunohistochemistry (c), and representative immunohistochemistry images of CD8⁺ effector T cells (d) in PDX-287R grafts after 48 h post-adoptive transfer with CAR T cells (n = 3 grafts/treatment). e, f Number of F4/80⁺ mouse macrophages per mm², based on immunohistochemistry (e), and representative immunohistochemistry images of F4/80⁺ mouse macrophages (f) in PDX-287R grafts after 48 h post-adoptive transfer of CAR T cells (n = 3 grafts/treatment). g–l Quantification and activation of CAR T cells in mice bearing PDX-287R grafts (g–i) and PDX-224R-Cx grafts (j–l) 48 h post-adoptive transfer of CAR T cells by flow cytometry. Compared to PDX-287R, PDX-224R-Cx had decreased sensitivity to carboplatin treatment alone, and a reduced response to carboplatin-CAR T cell combination treatment. g, j Number of CD3⁺CAR⁺ T cells extracted from blood, spleen, and tumor (TILs) in mice bearing PDX-287R (g) and PDX-224R-Cx (j; n = 6 mice/treatment for blood and spleen, n = 3 grafts/treatment for tumors). h, k Geometric mean fluorescence intensity (MFI) of CD25 and CD137 on TILs activated by anti-idiotype antibody of Le^Y CAR in PDX-287R (h) and PDX-224R-Cx (k; n = 3 tumors/treatment). i, l Percentage of IL-2-, TNF-α-, and IFN-γ-positive TILs activated by anti-idiotype antibody of Le^Y CAR using intracellular staining in PDX-287R (i) and PDX-224R-Cx (l; n = 3 tumors/treatment). Statistical significance in violin plots (a, c, e) was determined by one-way ANOVA with post-hoc Tukey’s test: a all groups vs carbo + CAR T, p < 0.0001; b no T cells vs carbo + CAR T, p = 0.0014; c carboplatin vs carbo + CAR T, p = 0.0033; d ev-T cells vs carbo + CAR T, p = 0.0008; e carbo + ev-T vs carbo + CAR T, p = 0.0011; f CAR T cells vs carbo + CAR T, p = 0.0010; g no T cells vs carbo + ev-T, p = 0.0048; h no T cells vs carbo + CAR T, p = 0.0003; i carboplatin vs carbo + CAR T, p = 0.0165; j ev-T cells vs carbo + ev-T, p = 0.0403; k ev-T cells vs carbo + CAR T, p = 0.0018; l CAR T cells vs carbo + ev-T, p = 0.0240; m CAR T cells vs carbo + CAR T, p = 0.0011. Data in g–l represents the mean ± SEM, and the significance was determined by two-tailed unpaired t test. ns not significant. Scale bars = 50 µm (b, d, f). Source data are provided as a Source Data file.