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Anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1(PD-L1) therapy frequently entails immune-related adverse events (irAEs), and biomarkers to predict irAEs are lacking. Although checkpoint inhibitors have been found to reinvigorate T cells, the relevance of autoantibodies remains elusive.
Our aim was to explore whether IgG autoantibodies directed against coexpressed antigens by tumor tissue and healthy skin correlate with skin irAEs and therapy outcome.
We measured skin-specific IgG via enzyme-linked immunosorbent assay in patients with non-small cell lung cancer (NSCLC) who received anti-PD1/PD-L1 treatment between July 2015 and September 2017 at the Kantonsspital St. Gallen. Sera were sampled at baseline and during therapy after 8 weeks.
Analysis of publicly available tumor expression data revealed that NSCLC and skin coexpress BP180, BP230, and type VII collagen. A skin irAE developed in 16 of 40 recruited patients (40%). Only elevated anti-BP180 IgG at baseline significantly correlated with the development of skin irAEs (P = .04), therapy response (P = .01), and overall survival (P = .04).
The patients were recruited in a single tertiary care center.
Our data suggest that the level of anti-BP180 IgG of NSCLC patients at baseline is associated with better therapy response and overall survival and with a higher probability to develop skin irAEs during anti-PD1/PD-L1 treatment.Le texte complet de cet article est disponible en PDF.
Key words : anti-PD1, autoantibodies, immune checkpoint inhibitors, immune-related adverse events, non-small cell lung cancer, skin rash
Abbreviations used : BP, ELISA, ICIs, irAE, LP, NSCLC, OS, PD1, PD-L1
| Funding sources: This work was supported the Swiss National Science Foundation (PP00P3_157448) to Dr Flatz; the Deutsche Forschungsgemeinschaft (Clinical Research Unit 303 Pemphigoid Diseases) and the Excellence Cluster “Inflammation at Interfaces” to Drs Schmidt, Zillikens, and Sadik; and the Forschungsförderung of the Kantonsspital St. Gallen to Dr Flatz.
| Conflicts of interest: Dr Zillikens has received research and development grants from Euroimmun Inc, Lübeck, Germany, for development of novel diagnostic test systems for autoantibodies in autoimmune bullous diseases, and Dr Schmidt has scientific cooperation with Euroimmun Inc.
| Reprints not available from the authors.