Immune profiling reveals the diverse nature of the immune response in NSCLC and reveals signaling pathways that may influence the anti-tumor immune response.

Abstract Recent FDA approvals of immunotherapy for NSCLC provide patients new treatment options, and these approvals also highlight the importance of the immune response in cancer treatment. While immunotherapy provides patients a new treatment option, the therapy is effective in less than half of the treated patients. To attain greater insight into the tumor-immune microenvironment, NSCLC tumors were analyzed by IHC and RNA-seq. IHC was used to identify NSCLC tumors that contain low, moderate, or high levels of CD8+ positive cells as a manifestation of an active anti-tumor immune response. Gene expression analysis identified an emergent gene signature that is associated with high and moderate levels of CD8 in NSCLC. In addition, the NSCLC tumors also express a unique combination of genes that may indicate complex anti-tumor immune responses (INFG-related genes, STATs, CXCL9, OX40, PD-L1, PD-L2, IDO1, and CD47). Several NSCLC tumors also express the immune checkpoint PD-L1 and at least one additional immune inhibitory molecule (IDO1, PD-L2, or others), which may explain the lack of a therapeutic response to treatments that disrupt only one immune checkpoint pathway.