Endoplasmic Reticulum Stress of Oral Squamous Cell Carcinoma Induces Immunosuppression of Neutrophils

Ching Fang Wu, Tzu Ting Hung, Yu Chieh Su, Po Jen Chen, Kuei Hung Lai, Chih Chun Wang

研究成果: 雜誌貢獻文章同行評審

摘要

The endoplasmic reticulum (ER) stress of cancer cells not only determined cancer cell fate but also indirectly triggered proinflammatory or immunosuppressive responses of macrophages. In addition, ER stressed neutrophils were known to acquire immunosuppressive activity with surface expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Since the importance of tumor ER stress and immunosuppressive neutrophils has been emphasized in head and neck cancers, we hypothesized that the ER stress of oral squamous cell carcinoma (OSCC) could transform neutrophils into LOX-1 expressing immunosuppressive phenotype. Two human OSCC cell lines, SCC25 and OML1, were treated with either vehicle or thapsigargin (THG), an ER stress inducer. These tumor conditioned media (TCM) were collected accordingly. Then human peripheral blood neutrophils from healthy donors were cultured in these TCM. The results showed that neutrophils cultured in THG-treated TCM had higher expression of LOX-1 compared with those cultured in vehicle-treated TCM. Moreover, by interleukin-2/anti-CD3/anti-CD28 activated autologous T cell proliferation assay, neutrophils conditioned by THG-treated TCM were shown to inhibit T cell proliferation more significantly than those conditioned by vehicle-treated TCM. These novel findings indicated that the ER stress of OSCC could be transmitted to neutrophils which in turn expressed LOX-1 and obtained immunosuppressive ability. Our findings further supported the existence of “transmissible” ER stress between tumor cells and neutrophils.
原文英語
文章編號818192
期刊Frontiers in Oncology
12
DOIs
出版狀態已發佈 - 3月 16 2022

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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