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

J Am Acad Dermatol. 2020 Apr;82(4):854-861. doi: 10.1016/j.jaad.2019.08.045. Epub 2019 Aug 23.

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.

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

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / adverse effects*
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Autoantigens / immunology*
  • Biomarkers / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Drug Eruptions / etiology*
  • Exanthema / chemically induced
  • Female
  • Humans
  • Immunoglobulin G / blood*
  • Lung Neoplasms / drug therapy*
  • Male
  • Non-Fibrillar Collagens / immunology*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Prospective Studies
  • Pruritus / chemically induced
  • Survival Analysis

Substances

  • Antineoplastic Agents, Immunological
  • Autoantigens
  • Biomarkers
  • Immunoglobulin G
  • Non-Fibrillar Collagens
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • collagen type XVII