The landscape of novel and complementary targets for immunotherapy: an analysis of gene expression in the tumor microenvironment.

Immunotherapies targeting immune checkpoint proteins CTLA-4, PD-1, and PD-L1 have saved lives, but these therapies have only been effective in some patients. Patients positive for expression of immune checkpoint proteins in the tumor microenvironment show better response to immune checkpoint inhibitors. Consequently, knowledge of which genes are consistently expressed in lymphocytes within the tumor microenvironment can convey potentially effective and complementary new immunotherapy targets. We identified 54 genes that have higher co-expression with the pan T-cell marker than or . In a dataset of 26 patients who received anti-PD-1 therapy, we observed that co-expression between and was higher among responders than non-responders, supporting our correlation-based approach. The genes highlighted in these analyses, which include , , , and , warrant further investigation of their therapeutic potential. We analyzed and ranked genes that were co-expressed with the pan T-cell marker in 9,601 human tumors, spanning 31 cancer types. To further identify targets that may be complementary to existing PD-1 therapy, we examined and ranked genes with high co-expression and relatively low co-expression.