Imaging of Immune Checkpoint Inhibitor Immunotherapy for Non–Small Cell Lung Cancer

The normal immune system identifies and eliminates precancer-ous and cancerous cells. However, tumors can develop immune resistance mechanisms, one of which involves the exploitation of pathways, termed immune checkpoints, that normally suppress T-cell function. The goal of immune checkpoint inhibitor (ICI) immu-notherapy is to boost T-cell–mediated immunity to mount a more effective attack on cancer cells. ICIs have changed the treatment landscape of advanced non–small cell lung cancer (NSCLC), and numerous ICIs have now been approved as first-line treatments for NSCLC by the U.S. Food and Drug Administration. ICIs can cause atypical response patterns such as pseudoprogression, whereby the tumor burden initially increases but then decreases. Therefore, response criteria have been developed specifically for patients receiving immunotherapy. Because ICIs activate the immune system, they can lead to inflammatory side effects, termed immune-related adverse events (irAEs). Usually occurring within weeks to months after the start of therapy, irAEs range from asymptomatic abnormal laboratory results to life-threatening conditions such as encephalitis, pneumonitis, myocarditis, hepatitis, and colitis. It is important to be aware of the imaging appearances of the various irAEs to avoid misinterpreting them as metastatic disease, progres-sive disease, or infection. The basic principles of ICI therapy; indi-cations for ICI therapy in the setting of NSCLC; response assess-ment and atypical response patterns of ICI therapy, as compared with conventional chemotherapy; and the spectrum of irAEs seen at imaging are reviewed.