J.C. Hassel, J. Mangana, R. Dummer, C. Pföhler, K. Wistuba-Hamprecht, B. Weide, L. Hakim-Meibodi1, F.
Meier, J. Roth, H.-D. Zucht, P. Budde, M. Tuschen, P. Schulz-Knappe
Conclusions
• Increased autoantibody reactivity precedes the onset of irAEs and colitis in melanoma patients
treated with anti-CTLA4 and/ or anti-PD-1 CPI.
• Autoantigens included classical tumor (MAGEB4, MAGED2, MUM1, TP53/p53, SAP17/CT22),
paraneoplastic (GPHN, AMPH) and few autoimmune antigens (RPLP2, RPLP0, LAMC1).
• Pathway analysis reveals that the identified antigens are at the cross-road between cancer and
immunity pathways including the sumoylation and ubiquitination pathways.
• The associated biological pathways and molecular functions suggest that autoantibodies
directed against tumor antigens and normal tissue antigens could be crossreactive leading to
autoimmunity by immune attack of normal tissues and organs.
• These autoantibodies may serve as useful biomarkers for a risk-based treatment decision.
Further validation work in multiple melanoma (MM) is ongoing.