Autoimmune antibodies correlate with immune checkpoint therapy-induced toxicities

Area of Science:

• Oncology
• Immunology
• Biomarker Discovery

Background:

• Immune checkpoint (IC) therapy offers significant cancer treatment benefits but can induce immune-related adverse events (irAEs).
• Predictive biomarkers for irAEs are needed to optimize patient management during IC therapy.

Purpose of the Study:

• To identify autoantibodies as predictive biomarkers for irAEs in patients undergoing IC therapy.
• To investigate the correlation between specific autoantibodies and the development of irAEs, such as hypophysitis and pneumonitis.

Main Methods:

• Serological analysis of recombinant cDNA expression libraries using plasma samples from IC-treated patients.
• Identification of autoantibodies in pre-treatment and on-treatment samples before irAE onset.
• Development and validation of an enzyme-linked immunosorbent assay (ELISA) to confirm findings in additional patient cohorts.

Main Results:

• Specific autoantibodies, including anti-GNAL and anti-ITM2B, were associated with immune-related hypophysitis.
• The anti-CD74 autoantibody was identified as a potential biomarker for immune-related pneumonitis.
• Autoantibodies were detected prior to the clinical manifestation of irAEs.

Conclusions:

• Autoantibodies show potential as predictive biomarkers for irAEs associated with IC therapy.
• Early detection of specific autoantibodies could facilitate proactive management strategies for irAEs.
• This research supports the development of serological tests for personalized IC therapy monitoring.