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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.

  • Author(s): Yu, Sebastian
  • Wu, Xuesong
  • Shi, Zhenrui
  • Huynh, Mindy
  • Jena, Prasant Kumar
  • Sheng, Lili
  • Zhou, Yan
  • Han, Dan
  • Wan, Yu-Jui Yvonne
  • Hwang, Samuel T
  • et al.

Published Web Location

https://pubmed.ncbi.nlm.nih.gov/32044178/
No data is associated with this publication.
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.

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