Omar Hasan Ali1, David Bomze2, Sandra S Ring2, Fiamma Berner2, Mirjam Fässler3, Stefan Diem4, Marie-Therese Abdou2, Christoph Hammers5, Shirin Emtenani6, Anne Braun6, Antonio Cozzio7, Bernhard Mani8, Wolfram Jochum9, Enno Schmidt5, Detlef Zillikens5, Christian D Sadik5, Lukas Flatz10. 1. Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland. 2. Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland. 3. Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Dermatology, Kantonsspital St. Gallen, St. Gallen, Switzerland. 4. Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Oncology and Hematology, Hospital of Grabs, Grabs, Switzerland. 5. Department of Dermatology, University of Lübeck, Lübeck, Germany; Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany; Center for Research on Inflammation of the Skin (CRIS), Lübeck, Germany. 6. Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany. 7. Department of Dermatology, Kantonsspital St. Gallen, St. Gallen, Switzerland. 8. Center of Laboratory Medicine, St. Gallen, Switzerland. 9. Institute of Pathology, Kantonsspital St. Gallen, St. Gallen, Switzerland. 10. Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Dermatology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland. Electronic address: lukas.flatz@kssg.ch.
Abstract
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). LIMITATIONS: The patients were recruited in a single tertiary care center. CONCLUSIONS: 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.
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). LIMITATIONS: The patients were recruited in a single tertiary care center. CONCLUSIONS: Our data suggest that the level of anti-BP180 IgG of NSCLCpatients 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.
Authors: Evelyn Wang; Lukas Kraehenbuehl; Kwami Ketosugbo; Jeffrey A Kern; Mario E Lacouture; Donald Y M Leung Journal: Ann Allergy Asthma Immunol Date: 2021-02-17 Impact factor: 6.248