Publications

BibTex format

@article{Condamine:2016:10.1126/sciimmunol.aaf8943,
author = {Condamine, T and Dominguez, GA and Youn, JI and Kossenkov, A and Mony, S and Alicea-Torres, K and Tsyganov, E and Hashimoto, A and Nefedova, Y and Lin, C and Partlova, S and Garfall, A and Vogl, DT and Xu, X and Knight, SC and Malietzsis, G and Lee, GH and Eruslanov, E and Albelda, SM and Wang, X and Mehta, JL and Bewtra, M and Rustgi, A and Hockstein, N and Witt, R and Masters, G and Nam, B and Smirnov, D and Sepulveda, MA and Gabrilovich, DI},
doi = {10.1126/sciimmunol.aaf8943},
journal = {Science Immunology},
title = {Lectin-type oxidized LDL receptor 1 defines a population of polymorphonuclear myeloid-derived suppressor cells in cancer patients},
url = {http://dx.doi.org/10.1126/sciimmunol.aaf8943},
volume = {1},
year = {2016}
}

Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are important regulators of immune responses in cancer and have been directly implicated in the promotion of tumor progression. However, the heterogeneity of these cells and the lack of distinct markers hamper the progress in understanding the biology and clinical importance of these cells. Using partial enrichment of PMN-MDSC with gradient centrifugation, we determined that low-density PMN-MDSC and high-density neutrophils from the same cancer patients had a distinct gene profile. The most prominent changes were observed in the expression of genes associated with endoplasmic reticulum (ER) stress. Unexpectedly, low-density lipoprotein (LDL) was one of the most increased regulators, and its receptor oxidized LDL receptor 1 (OLR1) was one of the most overexpressed genes in PMN-MDSC. Lectin-type oxidized LDL receptor-1 (LOX-1) encoded by OLR1 was practically undetectable in neutrophils in peripheral blood of healthy donors, whereas 5 to 15% of total neutrophils in cancer patients and 15 to 50% of neutrophils in tumor tissues were LOX-1+. In contrast to their LOX-1− counterparts, LOX-1+ neutrophils had gene signature, potent immunosuppressive activity, up-regulation of ER stress, and other biochemical characteristics of PMN-MDSCs. Moreover, induction of ER stress in neutrophils from healthy donors up-regulated LOX-1 expression and converted these cells to suppressive PMN-MDSCs. Thus, we identified a specific marker of human PMN-MDSC associated with ER stress and lipid metabolism, which provides new insights into the biology and potential therapeutic targeting of these cells.
AU  - Condamine,T
AU  - Dominguez,GA
AU  - Youn,JI
AU  - Kossenkov,A
AU  - Mony,S
AU  - Alicea-Torres,K
AU  - Tsyganov,E
AU  - Hashimoto,A
AU  - Nefedova,Y
AU  - Lin,C
AU  - Partlova,S
AU  - Garfall,A
AU  - Vogl,DT
AU  - Xu,X
AU  - Knight,SC
AU  - Malietzsis,G
AU  - Lee,GH
AU  - Eruslanov,E
AU  - Albelda,SM
AU  - Wang,X
AU  - Mehta,JL
AU  - Bewtra,M
AU  - Rustgi,A
AU  - Hockstein,N
AU  - Witt,R
AU  - Masters,G
AU  - Nam,B
AU  - Smirnov,D
AU  - Sepulveda,MA
AU  - Gabrilovich,DI
DO  - 10.1126/sciimmunol.aaf8943
PY  - 2016///
SN  - 2470-9468
TI  - Lectin-type oxidized LDL receptor 1 defines a population of polymorphonuclear myeloid-derived suppressor cells in cancer patients
T2  - Science Immunology
UR  - http://dx.doi.org/10.1126/sciimmunol.aaf8943
UR  - http://hdl.handle.net/10044/1/38764
VL  - 1
ER  -

Download

ProfessorStellaKnight

Contact

Assistant

Location

Summary

Citation

BibTex format

RIS format (EndNote, RefMan)