Diet-induced obesity exacerbates imiquimod-mediated psoriasiform dermatitis in anti-PD-1 antibody-treated mice: Implications for patients being treated with checkpoint inhibitors for cancer. Issue 3 (March 2020)

• Record Type: Journal Article
• Authors: Yu, Sebastian; Wu, Xuesong; Shi, Zhenrui; Huynh, Mindy; Jena, Prasant Kumar; Sheng, Lili; Zhou, Yan; Han, Dan; Wan, Yu-Jui Yvonne; Hwang, Samuel T.
• Is Part Of: Journal of dermatological science. Volume 97:Issue 3(2020)
• Page Start: 194
• Page End: 200
• Publication Date: 2020-03
• Subjects: APD1T anti-PD-1 therapy -- CD control diet -- GDL γδ low -- IL interleukin -- IMQ imiquimod -- ir-AEs immune-related adverse events -- PD-L1 programmed cell death protein ligand 1 -- PD-1 programmed cell death protein 1 -- PsD psoriasiform dermatitis -- WD Western diet; High-fat diet -- Immune checkpoint -- Psoriasis -- Sugar -- Western diet; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2020.01.011
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: Diet-induced obesity exacerbates imiquimoid-induced psoriasiform dermatitis in mice. Western diet (WD)-fed mice have more γδ low T cells and more PD-1 expressing γ δ low T cells than control diet-fed mice. WD-fed mice have a more exaggerated response to anti-PD-1 than lean mice in terms of IMQ-induced ear swelling, suggesting obesity could be a risk factor in the development of psoriasiform eruption during anti-PD-1 therapy. Abstract: Background: An ever-increasing number of cancer patients are being treated with checkpoint inhibitors such as anti-PD-1 antibodies, and a small percentage of these patients develop a psoriasis-like skin eruption or severe flares of prior psoriasis. Objective: We investigated the role of obesity in immune checkpoint inhibitors-exacerbated psoriasiform eruption. Methods: We fed female C57BL/6 mice a so-called Western diet (WD) or a control diet (CD). Imiquimod (IMQ) was applied topically on ears for 5 consecutive days to induce psoriasiform dermatitis (PsD). Psoriasis-related markers were examined by quantitative real-time PCR. Then we induced PsD in WD- and CD-fed mice in the presence or absence of systemic treatment of anti-PD-1 antibodies to examine if obese mice are more susceptible to anti-PD-1 related PsD than lean mice. Results: WD-fed mice showed higher baseline mRNA expression levels of psoriasis-associated cytokines such as IL-17, S100A8, and S100A9 compared to mice fed with CD. Furthermore, WD-fed mice had more γ δ low (GDL) T cells in the whole skin and higher expression of PD-1 on GDL T cells than CD-fed mice. WD-fed mice receiving anti-PD-1 had more prominent ear swelling than lean mice receiving anti-PD-1 during the 5-day IMQ course (2-fold increase, P < 0.0001 on day 5). Conclusion: WD-induced obesity enhances IMQ-induced psoriasiform inflammation. The finding that WD-fed mice have a more dramatic response to anti-PD-1 than lean mice in terms of IMQ-induced ear swelling suggests that obesity could be a risk factor in the development of psoriasiform eruption during anti-PD-1 therapy.