Fig. 6

The IPASS gene signature describes a complex immune network within paediatric cancers. A concept figure depicting the potential immune cell interactions which feature the IPASS genes. The IPASS describes interactions which both drive and control anti-tumour immunity. CD8⁺ T-cells (blue) recognise tumour-associated antigen on mature and cross-presenting dendritic cells (pink) [CD141, LAMP3] and secrete IFN-γ, which induces cancer cell MHC-I and PD-L1 expression. IFN-γ response genes [CXCL9, CXCL11] are derived from tumour associated macrophages (TAMs, mauve) and are key chemokines for trafficking of CXCR3⁺ effector T-cells into the tumour. Control over this effector T-cell trafficking is mediated by tumour cell secretion of LIF which suppresses TAM CXCL9. In addition, IL-10/STAT3 signalling in TAMs induces SBNO2, a transcriptional co-repressor which contributes to the anti-inflammatory response. The IPASS includes genes expressed by activated T-cells [NFATC3, NFKb1, CD27, CTLA4, GITR], in contrast to the immune suppressor Tregs (purple) constitutively express [GITR, CTLA4]. The functional effect of B7-H3 is context dependent, B7-H3 expression on tumour cells is immune suppressive. The transmembrane receptor FPR2 senses ligands from bacteria products and generates a danger signal. This figure was created in Biorender