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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


Ali, Omar Hasan; Bomze, David; Ring, Sandra; Berner, Fiamma; Fässler, Mirjam; Diem, Stefan; Abdou, Marie-Therese; Hammers, Christoph; Emtenani, Shirin; Braun, Anne; Cozzio, Antonio; Mani, Bernhard; Jochum, Wolfram; Schmidt, Enno; Zillikens, Detlef; Sadik, Christian D; Flatz, Lukas (2020). 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, 82(4):854-861.

Abstract

BACKGROUND: Anti-PD1/PD-L1 therapy frequently entails immune-related adverse events (irAEs) and biomarkers to predict irAEs are lacking. While checkpoint inhibitors have been found to re-invigorate T-cells, the relevance of autoantibodies remains elusive.
OBJECTIVE: Our aim was to explore whether IgG autoantibodies directed against co-expressed antigens by tumor tissue and healthy skin correlate with skin irAEs and therapy outcome.
METHODS: We measured skin-specific IgG via ELISA in non-small cell lung cancer (NSCLC) patients, 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 co-express BP180, BP230 and type VII collagen. Of 40 recruited patients, 16 (40%) developed a skin irAE. 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, overall survival and a higher probability to develop skin irAEs during anti-PD1/PD-L1 treatment.

Abstract

BACKGROUND: Anti-PD1/PD-L1 therapy frequently entails immune-related adverse events (irAEs) and biomarkers to predict irAEs are lacking. While checkpoint inhibitors have been found to re-invigorate T-cells, the relevance of autoantibodies remains elusive.
OBJECTIVE: Our aim was to explore whether IgG autoantibodies directed against co-expressed antigens by tumor tissue and healthy skin correlate with skin irAEs and therapy outcome.
METHODS: We measured skin-specific IgG via ELISA in non-small cell lung cancer (NSCLC) patients, 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 co-express BP180, BP230 and type VII collagen. Of 40 recruited patients, 16 (40%) developed a skin irAE. 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, overall survival and a higher probability to develop skin irAEs during anti-PD1/PD-L1 treatment.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Dermatology
Language:English
Date:1 April 2020
Deposited On:28 Aug 2019 13:16
Last Modified:14 Mar 2020 02:02
Publisher:Elsevier
ISSN:0190-9622
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.jaad.2019.08.045
PubMed ID:31449902

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