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 journalArticlepeer-review

118 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

Fingerprint Dive into the research topics of 'The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors'. Together they form a unique fingerprint.

Cite this