Vascular E-selectin Expression Recognized by the U12-12 Monoclonal Antibody as a Predictive Marker for Steroid Resistance in Immune Checkpoint Inhibitor-related Colitis.

Abstract

In immune checkpoint inhibitor (ICI)-related colitis, tumor necrosis factor (TNF)-α blockade is recommended if symptoms are not alleviated with corticosteroids. Although TNF has been shown to be associated with steroid resistance, the early prediction of steroid resistance is challenging in clinical practice. Therefore, in the present study, we evaluated the potential of vascular E-selectin expression, which is induced by TNF, to serve as a predictor of steroid resistance in ICI-related colitis. We performed immunohistochemical analysis of 29 cases of ICI-related colitis using the U12-12 monoclonal antibody, which specifically recognizes E-selectin, and examined the association between U12-12 staining and clinical features. The result showed that the proportion of steroid-resistant cases was significantly higher in the U12-12-positive group (8 of 9 cases; 88.9%) than in the U12-12-negative group (1 of 20 cases; 5.0%) (p<0.001). Furthermore, the proportion of steroid-resistant cases was 100% (6 of 6 cases) in patients with U12-12-positive and Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher and 0% (0 of 12 cases) in patients with U12-12-negativity and CTCAE grade 1 or 2. Thus, evaluation of vascular E-selectin expression using the U12-12 monoclonal antibody is useful for predicting steroid resistance in ICI-related colitis.