Fig. 3: FAP-CAR T cells overcome the physical barrier and immunosuppressive TME to infiltrate tumor nests. | Nature Communications

Fig. 3: FAP-CAR T cells overcome the physical barrier and immunosuppressive TME to infiltrate tumor nests.

From: Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors

Fig. 3

a Workflow for two-photon microscopy. b Representative two-photon images at subregions of tumors treated with MigR, Meso-CAR, or FAP-CAR T cells at indicated timepoints. GFP+ T cells (green, red arrows), stromal cells (magenta), tumor cells (cyan), and SHG (gray). Scale bar, 100 µm. c Quantification of GFP+ T cells, stromal cells, SHG fiber number, and SHG+ area in stroma-rich (left) and tumor nests (right) at indicated timepoints. d Quantification of T cell motility (left; mean track speed; middle, track length; right, track straightness) for MigR, Meso-CAR, and FAP-CAR T cells at day 7 post-administration. e Quantification of FAP-CAR T cell mobility in stroma-rich (top) and tumor nest (bottom) regions at indicated timepoints. a Created with BioRender.com. Data points (15 per condition) in c represent measurements in 3 different fields of stroma-rich and 3 different fields of tumor-nest regions from tumor slices from 5 mice per group. Data points in d, e represent the quantification of motility of all individual T cells (identified unbiasedly by Imaris) in the 3 most stroma-rich regions and the 3 most tumor cell-rich (nest) regions amongst 6 systematically selected fields for one slice from each of 5 tumors per group; bars, mean ± SD. Groups were compared using two-way ANOVA with Tukey’s multiple comparisons tests (c) or one-way ANOVA analysis with Dunnett’s multiple comparison tests d, e. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. c T cells (left): Day 1 MigR/Meso-CAR vs. FAP-CAR, p = 0.003 and 0.004, respectively. Fiber number: left Day 4 MigR/Meso-CAR vs. FAP-CAR, p = 0.004 and 0.013, respectively; right Day 7 MigR/Meso-CAR vs. FAP-CAR, p = 0.001 and 0.007, respectively. SHG area (right): Day 7 MigR vs. FAP-CAR, p = 0.004. d. track speed: MigR/Meso-CAR vs. FAP-CAR, p = 0.002 and 0.012, respectively. e track straightness (left): Day 4 vs. 7, p = 0.009. The p values for remaining comparisons are all <0.001 or <0.0001. Source data are provided as a Source Data file.

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