The mechanism and risk factors for immune checkpoint inhibitor pneumonitis in non-small cell lung cancer patients

Abstract

Immune checkpoint inhibitors (ICIs) are new and promising therapeutic agents for non-small cell lung cancer (NSCLC). However, along with demonstrating remarkable efficacy, ICIs can also trigger immune-related adverse events. Checkpoint inhibitor pneumonitis (CIP) has been reported to have a morbidity rate of 3% to 5% and a mortality rate of 10% to 17%. Moreover, the incidence of CIP in NSCLC is higher than that in other tumor types, reaching 7% to 13%. With the increased use of ICIs in NSCLC, CIP has drawn extensive attention from oncologists and cancer researchers. Identifying high risk factors for CIP and the potential mechanism of CIP are key points in preventing and monitoring serious adverse events. In this review, the results of our analysis and summary of previous studies suggested that the risk factors for CIP may include previous lung disease, prior thoracic irradiation, and combinations with other drugs. Our review also explored potential mechanisms closely related to CIP, including increased T cell activity against associated antigens in tumor and normal tissues, preexisting autoantibodies, and inflammatory cytokines.