Fig. 4

Components of the tumor inflammatory signature as assessed by immune cell gene expression profiling. a Complex interplay of chemokines and cytokines classify the inflammatory state of the tumor microenvironment. Interferon-g (IFN-g) released by activated T cells and NK cells activates STAT1, IDO-1 (indolamine oxygenase I) and CMKLR1 in dendritic cells and macrophages (1). STAT-1 mediated signaling and additional pathways produce the chemokines CCL5 and CXCL9 (2). This recruits additional T cells into the tumor microenviroment through CXCR6. IFN-g stimulates the expression of HLA molecules and proteasome components including PSMB10 (3). Finally, IFN-g upregulates a number of immune checkpoint molecules including PD-L1, PD-L2, TIGIT, LAG-3, and B7-H3 on T cells (4). b Components of 18-gene immune signature under evaluation in prospective trials with pembrolizumab