Issues

Akbay and colleagues found that EGFR activation in non–small cell lung cancer (NSCLC) resulted in an immunosuppressive microenvironment characterized by upregulation of programmed cell death 1 (PD-1) and its ligand PD-L1, reduction of CD8⁺ cytotoxic T cells, and induction of tumor-promoting cytokines. PD-1 blockade suppressed EGFR-driven NSCLC growth via increased T-cell infiltration and improved cytotoxic T-cell function, as well as reduced expression of immunosuppressive cytokines. PD-L1 induction in human NSCLC cells was dependent on EGFR activation, as treatment with EGFR kinase inhibitors decreased PD-L1 levels. These results define a non–cell-autonomous role of oncogenic EGFR in promoting immune evasion in lung cancer and suggest that dual inhibition of EGFR and PD-1 may be effective in EGFR-mutant NSCLC. For details, please see the article by Akbay and colleagues on page 1355.