Ustekinumab Improves Psoriasis without Suppressing Tumor Antigen-Specific Cytotoxic T Lymphocytes

Abstract

Background: Ustekinumab is currently used for the treatment of psoriasis with remarkable efficiency. However, worries about the development of malignancies in ustekinumab-treated patients have not been completely resolved because of the major role of IL-12 and IL-23 in tumor immunity. In the present study, we tried to elucidate the effects of ustekinumab on antigen-specific tumor immunity. Methods: After approval by the institutional ethical committee, a 56-year-old male volunteer with psoriasis was administered with 20 doses of WT1 peptide. WT1-specific cytotoxic T lymphocytes (CTLs) were evaluated by WT1 tetramer assay after mixed lymphocyte peptide culture. Results: WT1 tetramer+ T cells with cytotoxic ability appeared in the blood after peptide administration and the frequency of WT1 tetramer+ T cells increased to more than 15 in 10⁶ CD8+ T cells. Thirty months after stopping WT1 administration, the patient commenced treatment with ustekinumab for psoriasis at weeks 0 and 4, and every 12 weeks thereafter. Psoriasis plaques were almost cleared up and the response to ustekinumab has so far lasted for 30 months. The frequency of WT1 tetramer+ T cells has not changed since the initiation of ustekinumab treatment. The effects of ustekinumab on the antigen-presenting and CTL-inducing abilities of dendritic cells were explored in vitro, revealing limited effects on both immune functions. Conclusions: These in vivo/vitro findings imply that ustekinumab improves psoriasis without suppressing tumor antigen-specific CTLs and support the data of recent clinical trials showing no increased incidence of malignancies with ustekinumab treatment.

Reactive Oxygen Species in Psoriasis and Psoriasis Arthritis: Relevance to Human Disease

“…Ustekinumab binds specifically to IL-12/IL-23p40 and thus effectively neutralizes their biological activity. Recent findings imply that ustekinumab treatment improves Ps without suppressing tumor antigen-specific cytotoxic T lymphocytes, supporting clinical trials showing no increased incidence of malignancies with ustekinumab treatment [96]. IL-23 has been shown to activate T cells expressing a different cytokine profile such as IL-17A and IL-17F (termed Th17 cells) and an IL-22-expressing T-cell subset (called Th22).…”

Depression and Insomnia in Patients With Psoriasis and Psoriatic Arthritis Taking Tumor Necrosis Factor Antagonists

“… 1 Low self esteem, social anxiety, embarrassment due to disease stigmata, or absence from work due to painful arthritis may partly explain the psycho-social impact of psoriasis. The prevalence rates of psychological symptoms in psoriasis have been reported to be higher than in many other disfiguring skin diseases 2 and as high as in other major medical diseases, including myocardial infarction, diabetes, hypertension, and cancer. 3 …”