Immune-related Pulmonary Toxicity From Cancer Immunotherapy: A Systematic Approach

Immune checkpoint inhibitors (ICIs) are one of the major advances in cancer treatment. ICIs have shown significant benefit in treating several types of cancer. Currently there are 6 ICIs available in the United States and multiple ICIs in the pipeline. Immune checkpoint signaling leads to immune tolerance of cancer cells through downregulation of T-cell activation. The reversal in tumor-tolerance and self-tolerance effected by ICIs likely drives both T-cell–mediated toxicity and immune-related adverse effects (irAEs); however, the exact mechanism remains not completely understood. Pulmonary irAEs are among the most feared high-grade irAEs leading to discontinuation of ICIs and, not uncommonly, treatment-related death. Because of the high degree of morbidity and mortality associated with pulmonary irAEs and the exponential growth of ICI use, clinicians must increasingly be facile in diagnosing and managing these irAEs.