Autoimmune antibodies correlate with immune checkpoint therapy-induced toxicities
Menée à partir d'échantillons plasmatiques prélevés sur des patients atteints d'un cancer traité par inhibiteur de point de contrôle immunitaire, cette étude met en évidence une corrélation entre la présence d'auto-anticorps et les toxicités induites par le traitement
A substantial portion of cancer patients treated by immune checkpoint (IC) therapy develop immune-related adverse events (irAEs), which result in significant morbidity and mortality. We sought to understand the mechanisms of these irAEs and to identify biomarkers to predict irAEs to maximize the clinical benefits of IC therapy. We screened plasma samples from patients who developed IC therapy-induced hypophysitis or pneumonitis against a cDNA expression library of the brain or lungs and directly identified autoimmune antibodies correlating with hypophysitis or pneumonitis. Our data suggest that these autoantibodies correlate with hypophysitis or pneumonitis and should be tested as the first predictive biomarkers for early detection, timely treatment, and close monitoring of these 2 potentially fatal irAEs.Immune checkpoint (IC) therapy provides substantial benefits to cancer patients but can also cause distinctive toxicities termed immune-related adverse events (irAEs). Biomarkers to predict toxicities will be necessary to improve management of patients receiving IC therapy. We relied on serological analysis of recombinant cDNA expression libraries to evaluate plasma samples from patients treated with IC therapy and identified autoantibodies, both in pretreatment and on-treatment samples prior to the development of irAEs, which correlate with the development of immune-related hypophysitis (anti-GNAL and anti-ITM2B autoantibodies) and pneumonitis (anti-CD74 autoantibody). We developed an enzyme-linked immunosorbent assay and tested additional patient samples to confirm our initial findings. Collectively, our data suggest that autoantibodies may correlate with irAEs related to IC therapy, and specific autoantibodies may be detected early for the management of irAEs.
Proceedings of the National Academy of Sciences , résumé, 2018