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

81 Citations (Scopus)

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

Fingerprint

Transcription Factor CHOP
Neoplasms
Interleukin-6
Activating Transcription Factor 4
CCAAT-Enhancer-Binding Proteins
Reactive Nitrogen Species
Myeloid-Derived Suppressor Cells
Immunotherapy
Immunity
Reactive Oxygen Species

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Thevenot, P. T., Sierra, R. A., Raber, P. L., Al-Khami, A. A., Trillo-Tinoco, J., Zarreii, P., ... 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

The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors. / Thevenot, Paul T.; Sierra, Rosa A.; Raber, Patrick L.; Al-Khami, Amir A.; Trillo-Tinoco, Jimena; Zarreii, Parisa; Ochoa, Augusto C.; Cui, Yan; DelValle, Luis; Rodriguez, Paulo C.

In: Immunity, Vol. 41, No. 3, 18.09.2014, p. 389-401.

Research output: Contribution to journalArticle

Thevenot, PT, Sierra, RA, Raber, PL, Al-Khami, AA, Trillo-Tinoco, J, Zarreii, P, Ochoa, AC, Cui, Y, DelValle, L & Rodriguez, PC 2014, 'The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors', Immunity, vol. 41, no. 3, pp. 389-401. https://doi.org/10.1016/j.immuni.2014.08.015
Thevenot, Paul T. ; Sierra, Rosa A. ; Raber, Patrick L. ; Al-Khami, Amir A. ; Trillo-Tinoco, Jimena ; Zarreii, Parisa ; Ochoa, Augusto C. ; Cui, Yan ; DelValle, Luis ; Rodriguez, Paulo C. / The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors. In: Immunity. 2014 ; Vol. 41, No. 3. pp. 389-401.
@article{f6fa31e812324545a105d172ba838003,
title = "The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors",
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.",
author = "Thevenot, {Paul T.} and Sierra, {Rosa A.} and Raber, {Patrick L.} and Al-Khami, {Amir A.} and Jimena Trillo-Tinoco and Parisa Zarreii and Ochoa, {Augusto C.} and Yan Cui and Luis DelValle and Rodriguez, {Paulo C.}",
year = "2014",
month = "9",
day = "18",
doi = "10.1016/j.immuni.2014.08.015",
language = "English (US)",
volume = "41",
pages = "389--401",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors

AU - Thevenot, Paul T.

AU - Sierra, Rosa A.

AU - Raber, Patrick L.

AU - Al-Khami, Amir A.

AU - Trillo-Tinoco, Jimena

AU - Zarreii, Parisa

AU - Ochoa, Augusto C.

AU - Cui, Yan

AU - DelValle, Luis

AU - Rodriguez, Paulo C.

PY - 2014/9/18

Y1 - 2014/9/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84908003234&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908003234&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2014.08.015

DO - 10.1016/j.immuni.2014.08.015

M3 - Article

VL - 41

SP - 389

EP - 401

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 3

ER -