Autoantibody Development under Treatment with Immune-Checkpoint Inhibitors

Cancer Immunol Res. 2019 Jan;7(1):6-11. doi: 10.1158/2326-6066.CIR-18-0245. Epub 2018 Nov 13.

Abstract

Immune-checkpoint inhibitors (ICIs) activate the immune system to assault cancer cells in a manner that is not antigen specific. We hypothesized that tolerance may also be broken to autoantigens, resulting in autoantibody formation, which could be associated with immune-related adverse events (irAEs) and antitumor efficacy. Twenty-three common clinical autoantibodies in pre- and posttreatment sera from 133 ipilimumab-treated melanoma patients were determined, and their development linked to the occurrence of irAEs, best overall response, and survival. Autoantibodies developed in 19.2% (19/99) of patients who were autoantibody-negative pretreatment. A nonsignificant association was observed between development of any autoantibodies and any irAEs [OR, 2.92; 95% confidence interval (CI) 0.85-10.01]. Patients with antithyroid antibodies after ipilimumab had significantly more thyroid dysfunction under subsequent anti-PD-1 therapy: 7/11 (54.6%) patients with antithyroid antibodies after ipilimumab developed thyroid dysfunction under anti-PD1 versus 7/49 (14.3%) patients without antibodies (OR, 9.96; 95% CI, 1.94-51.1). Patients who developed autoantibodies showed a trend for better survival (HR for all-cause death: 0.66; 95% CI, 0.34-1.26) and therapy response (OR, 2.64; 95% CI, 0.85-8.16). We conclude that autoantibodies develop under ipilimumab treatment and could be a potential marker of ICI toxicity and efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Autoantibodies / blood*
  • Biomarkers / blood
  • CTLA-4 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / immunology
  • Female
  • Humans
  • Ipilimumab / adverse effects
  • Ipilimumab / therapeutic use*
  • Male
  • Melanoma / blood
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Middle Aged
  • Skin Neoplasms / blood
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / immunology
  • Thyroid Gland / drug effects
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Immunological
  • Autoantibodies
  • Biomarkers
  • CTLA-4 Antigen
  • Ipilimumab