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. 2024 Feb 12;42(2):283–300.e8. doi: 10.1016/j.ccell.2023.12.008

Figure 8.

Figure 8

TIGIT blockade improves survival in a chemotherapy-resistant neuroblastoma model

(A) Graphic representation of study setup, adding anti-TIGIT and/or PD-L1 to the standard relapse backbone treatment (Temozolomide/Irinotecan (TEM/IRI) + anti-GD2) in a chemotherapy-resistant, immunologically cold model.

(B) Treatment schedule for mice with small tumors.

(C) Survival analysis in mice with small tumors. T/I = TEM/IRI, aGD2 = anti-GD2, aTIG = anti-TIGIT, aPD-L1 = anti-PD-L1. N = 7 mice per group. Matched analysis, log rank (Mantel-Cox) test.

(D) Tumor volume measured over time in mice with small tumors. N = 7 mice per group. Linear Mixed-Effects Models. Right panel: detailed view of tumor volumes on days 0–5.

(E) Treatment schedule for mice with large tumors.

(F) Survival analysis in mice with large tumors treated with vehicle (n = 3), TEM/IRI + anti-GD2 (n = 6) or TEM/IRI + anti-GD2 + anti-TIGIT (n = 4). Matched analysis, log rank (Mantel-Cox) test.

(G) Tumor volume measured over time in mice with large tumors treated with vehicle (n = 3), TEM/IRI + anti-GD2 (n = 6) or TEM/IRI + anti-GD2 + anti-TIGIT (n = 4). Linear Mixed-Effects Models. Right panel: detailed view of tumor volumes on days 0–5. (H–J) Flow cytometric analysis of TME in small and large tumors (vehicle condition). N = 4 animals per condition.

(H-J) High-dimensional flow cytometry comparing immune environment in large and small tumors. (H) TNSE representation of TME and percentage of CD45+ cells. Mann Whitney U test.

(I) Detailed immune cell, macrophage, and T cell composition in small and large tumors. ∗p < 0.05 between small and large,#0.05<p < 0.1 between small and large. Two-way ANOVA.

(J) Immune cell populations as percentage of total live cells (vehicle condition). Mann Whitney U test.

(K) TIGIT and PDCD1 expression in single-cell RNA sequencing data (extracted from R2 (r2.amc.nl; Metelitsa–124509–Seurat_cp10k–GSE223071), of isolated CAR-NKT cells (infusion products) pre- and post-infusion into neuroblastoma patients, in responding and non-responding patients58. Two-way ANOVA. ∗∗∗p < 0.001, ∗p < 0.05. Boxplot represents mean, min, and max. Also see Figure S9.