Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 44, Pages 22246-22251Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1908079116
Keywords
hypophysitis; pneumonitis; autoimmune antibody; immune checkpoint therapy; immune-related adverse events
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Funding
- MD Anderson Cancer Center Immunotherapy Platform
- MD Anderson Physician Scientist Award
- Khalifa Physician Scientist Award
- Andrew Sabin Family Foundation
- Doris Duke Charitable Foundation
- Wendy and Leslie Irvin Barnhart Fund
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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.
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