The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors

Paul T. Thevenot, Rosa A. Sierra, Patrick L. Raber, Amir A. Al-Khami, Jimena Trillo-Tinoco, Parisa Zarreii, Augusto C. Ochoa, Yan Cui, Luis DelValle, Paulo C. Rodriguez

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Adaptation of malignant cells to the hostile milieu present in tumors is an important determinant of their survival and growth. However, the interaction between tumor-linked stress and antitumor immunity remains poorly characterized. Here, we show the critical role of the cellular stress sensor C/EBP-homologous protein (Chop) in the accumulation and immune inhibitory activity of tumor-infiltrating myeloid-derived suppressor cells (MDSCs). MDSCs lacking Chop had decreased immune-regulatory functions and showed the ability to prime Tcell function and induce antitumor responses. Chop expression in MDSCs was induced by tumor-linked reactive oxygen and nitrogen species and regulated by the activating-transcription factor-4. Chop-deficient MDSCs displayed reduced signaling through CCAAT/enhancer-binding protein-β, leading to a decreased production of interleukin-6 (IL-6) and low expression of phospho-STAT3. IL-6 overexpression restored immune-suppressive activity of Chop-deficient MDSCs. These findings suggest the role of Chop in tumor-induced tolerance and the therapeutic potential of targeting Chop in MDSCs for cancer immunotherapy.

Original languageEnglish (US)
Pages (from-to)389-401
Number of pages13
JournalImmunity
Volume41
Issue number3
DOIs
StatePublished - Sep 18 2014
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Thevenot, P. T., Sierra, R. A., Raber, P. L., Al-Khami, A. A., Trillo-Tinoco, J., Zarreii, P., Ochoa, A. C., Cui, Y., DelValle, L., & Rodriguez, P. C. (2014). The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors. Immunity, 41(3), 389-401. https://doi.org/10.1016/j.immuni.2014.08.015