Figure 6.

Targetable immunoregulatory interactions in neuroblastoma

(A) Graphical representation of analysis strategy for Figure 6B: selection of genes (“B”) expressed by population “X” which are involved in a significant ligand-receptor interaction between population “X” and T cell subset “Y”, of which the expression by population “X” also significantly correlates with the dysfunction score of T cell subset “Y”. Genes with at least one significant correlation, with either DUSP4^hi CD4 or CD8 T, were included.

(B) Heatmap showing Pearson correlation of expression of genes “B” by populations “X” with dysfunction score of T cell subsets “Y”.

(C) All predicted NECTIN2-TIGIT interactions with DUSP4^hi CD4 and CD8 T cells in neuroblastoma.

(D) Flow cytometric validation of nectin-2 protein expression on neuroblastoma tumor samples. Mean ± SD.

(E) Flow cytometric validation of TIGIT protein expression on T cell populations infiltrating neuroblastoma, compared to reference T cells from blood (PB). TPT1^hi CD4 were gated as IL-7R^hiPD-1^lo CD4⁺ cells and DUSP4^hi CD4 were gated as IL-7R^loPD-1^hi CD4⁺ cells, as shown in Figure 3F. Two-way ANOVA with Sidak’s post-hoc test. Mean ± SD.

(F) Correlation of NECTIN2 gene expression with dysfunction score in bulk-RNAseq dataset of SEQC cohort consisting of 498 neuroblastomas (r2.amc.nl; Tumor Neuroblastoma–SEQC–498–RPM–seqcnb1; GSE49710). Also see Figure S7.