BP180-specific IgG is associated with skin adverse events, therapy response, and overall survival in non-small cell lung cancer patients treated with checkpoint inhibitors

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

卷:82

Article

Ali, Omar Hasan^1,2  Bomze, David²  Ring, Sandra S.²  Berner, Fiamma²  Fassler, Mirjam^2,3  Diem, Stefan^2,4,5  Abdou, Marie-Therese²  Hammers, Christoph^6,7,8  Emtenani, Shirin⁷  Braun, Anne⁷  Cozzio, Antonio³  Mani, Bernhard⁹  Jochum, Wolfram¹⁰  Schmidt, Enno^6,7,8  Zillikens, Detlef^6,7,8  Sadik, Christian D.^6,7,8  Flatz, Lukas^1,2,3,4 

[1] Univ Hosp Zurich, Dept Dermatol, Zurich, Switzerland

[2] Kantonsspital St Gallen, Inst Immunobiol, St Gallen, Switzerland

[3] Kantonsspital St Gallen, Dept Dermatol, Rorschacher Str 95, CH-9007 St Gallen, Switzerland

[4] Kantonsspital St Gallen, Dept Hematol & Oncol, St Gallen, Switzerland

[5] Hosp Grabs, Dept Hematol & Oncol, Grabs, Switzerland

[6] Univ Lubeck, Dept Dermatol, Lubeck, Germany

[7] Univ Lubeck, Lubeck Inst Expt Dermatol, Lubeck, Germany

[8] CRIS, Lubeck, Germany

[9] Ctr Lab Med, St Gallen, Switzerland

[10] Kantonsspital St Gallen, Inst Pathol, St Gallen, Switzerland

关键词: anti-PD1;    autoantibodies;    immune checkpoint inhibitors;    immune-related adverse events;    non-small cell lung cancer;    skin rash;   

DOI  :  10.1016/j.jaad.2019.08.045

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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