Fig. 7: FAP-CAR T cells rendered tumors permissive to Meso-CAR T cells allowing their infiltration and function within tumor. | Nature Communications

Fig. 7: FAP-CAR T cells rendered tumors permissive to Meso-CAR T cells allowing their infiltration and function within tumor.

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

Fig. 7

a Treatment protocol: 4662 tumor-bearing CD45.1 C57BL/6 mice (hosts) were treated with donor MigR control, Meso-CAR or FAP-CAR T cells (CD45.2 GFP+). 4 days later, all mice received a second treatment of CD45.2 tdTomato+ Meso-CAR T cells. b Representative static images from two-photon microscopy at different subregions in the tumors treated with MigR control, Meso-CAR, or FAP-CAR T cells (GFP+) with subsequent Meso-CAR T cells (tdTomato+) at indicated time points. The GFP+ T cells from first treatment appear green and tdTomato+ Meso-CAR T cells from second treatment appear red and examples of latter are highlighted by white arrows. CD90.2+ stromal cells appear magenta and mCerulean+ tumor cells cyan. Scale bar, 100 µm. c Quantification of tdTomato+ Meso-CAR T cells (Top panels) and mCerulean+ tumor cells (bottom panels) in stroma-rich (left) and tumor nest (right) regions at day 1, 4 and 7 post administration. Data points (15 per condition) 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. d Representative flow plots and quantification of flow cytometry analysis of tdTomato+ Meso-CAR T cells in tumors from the indicated treatment groups at the indicated times post-second treatment. e Quantification of the expression of GzmB, IFN-γ and TNF-α by examined for the infiltrating tdTomato+ Meso-CAR T cells in tumors from each of the indicated treatment groups at the indicated times post-second treatment. Data points are mean±SD (n = 5 per group) and groups were compared using two-way ANOVA with Tukey’s multiple comparisons tests (c, d) or one-way ANOVA analysis with Dunnett’s multiple comparison tests (e). *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. c % mCerulean+ tumor cell: Day 1 MigR+Meso-CAR/Meso-CAR+Meso-CAR vs. FAP-CAR+Meso-CAR, p = 0.001 and 0.031, respectively. Day 7 Meso-CAR+Meso-CAR vs. FAP-CAR+Meso-CAR, p = 0.004. 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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