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

Sebastian Yu, Xuesong Wu, Zhenrui Shi, Mindy Huynh, Prasant Kumar Jena, Lili Sheng, Yan Zhou, Dan Han, Yu Jui Yvonne Wan, Samuel T. Hwang

Research output: Contribution to journalArticle

3 Scopus citations

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 γδ 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.

Original languageEnglish (US)
JournalJournal of Dermatological Science
DOIs
StateAccepted/In press - Jan 1 2020

Keywords

  • High-fat diet
  • Immune checkpoint
  • Psoriasis
  • Sugar
  • Western diet

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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