Immunopathophysiology of immune checkpoint inhibitor-related pneumonitis: insights from multi-omics and immune...

Although immune checkpoint inhibitors (ICIs) have demonstrated groundbreaking effectiveness in cancer treatment, they carry the risk of immune-related adverse events, including interstitial pneumonia (ICI-pneumonitis), a potentially life-threatening pulmonary complication. Comprehensive immune analyses of peripheral blood, bronchoalveolar lavage fluid, and lung tissue have demonstrated that ICI-pneumonitis results from excessive activation and proliferation of cytotoxic T lymphocytes and helper T cells, suppression of regulatory T cells, and increased secretion of pro-inflammatory cytokines. The dysregulation of innate immune cells also contributes to the formation of a complex immune microenvironment. Bronchoalveolar lavage fluid analyses revealed a lymphocyte-rich cell population dominated by CD8⁺ T cells and CD4⁺ types 1 and 17 helper T cells. Studies on lung tissues using spatial transcriptomics and imaging mass cytometry have provided detailed insights into the inflammatory microenvironment. These studies enhance our understanding of the intricate relationships between immune cells and the mechanisms underlying pulmonary tissue injury. Integrating multi-omics data will provide new insights into the immuno-pathophysiology of ICI-pneumonitis, deepening our understanding of this condition. These insights will enable more precise individual risk assessments and facilitate the development of safer immunotherapeutic strategies. This review highlights the recent research findings and provides an overview of the immunopathophysiology of ICI-pneumonitis.