Autoantibody development under treatment with immune checkpoint inhibitors.

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 post-treatment 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 pre-treatment. A non-significant association was observed between development of any autoantibodies and any irAEs (OR: 2.92 [95% CI: 0.85 to 10.01]). Patients with anti-thyroid antibodies after ipilimumab had significantly more thyroid dysfunction under subsequent anti-PD-1 therapy: 7/11 (54.6%) patients with anti-thyroid antibodies after ipilimumab developed thyroid dysfunction under anti-PD1 versus 7/49 (14.3%) patients without antibodies (OR: 9.96 [95% CI: 1.94 to 51.1]). Patients who developed autoantibodies showed a trend for better survival (HR for all-cause death: 0.66 [95% CI: 0.34 to 1.26]) and therapy response (OR: 2.64 [95% CI: 0.85 to 8.16]). We conclude that autoantibodies develop under ipilimumab treatment and could be a potential marker of ICI toxicity and efficacy.