Fig. 2: DSF/Cu + IR-stressed cancer cells drive phenotypic switch in CAR T cells with early memory-like characteristics. | Nature Communications

Fig. 2: DSF/Cu + IR-stressed cancer cells drive phenotypic switch in CAR T cells with early memory-like characteristics.

From: Stressed target cancer cells drive nongenetic reprogramming of CAR T cells and solid tumor microenvironment

Fig. 2

a The heatmap shows differences in memory T-cell-associated genes between B7-H3 CAR T cells co-cultured with non-stressed SUM159 tumor cells vs. DSF/Cu+IR-stressed cells (n = 3 biologically independent experiments). be Phenotypic analysis of CAR T cells with markers CD45RA and CD62L after in vitro reprogramming by 72 h co-cultured with target cells: SUM149 (b), SUM159 (c), PANC-1 (d) or PCI-13 (e). The frequencies of stem cell memory (TSCM, CD45RA+CD62L+), central memory (TCM, CD45RA-CD62L+), effector memory (TEM, CD45RA-CD62L-), and effector (TEFF, CD45RA+CD62L-) T cells in different groups are shown (n = 4 independent experiments). f The number of in vitro expanded CAR T cells from metastatic breast cancer patient-derived PBMCs show higher preexisting percentages of TSCM (n = 10 individual donors) vs. lower percentages of TSCM (n = 10 individual donors) after reprogramming by 72 h co-cultured with stressed vs. non-stressed target cells (n = 10 individual donors). g Positive correlation between in vitro expansion capacity of CAR T cells and preexisting percentage of TSCM cells in PBMCs (n = 20 individual donors). Statistical comparisons were performed using two-way ANOVA with Sidak’s multiple comparisons test (b, c, d, e), one-way ANOVA with Tukey’s multiple comparisons test (f), and two-tailed Pearson’s r correlation (g). P-values are shown and error bars indicate mean ± SD. ns represents no significant difference. Source data are provided as a Source Data file.

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