Mechanism regulating reactive oxygen species in tumor induced myeloid-derived suppressor cells

By Cesar A. Corzo, M. Cotter, P. Cheng, Fendong Cheng, S. Kusmartsev, E. Sotomayor, T. Padhya, T. Mccaffrey, J. Mccaffrey, D. Gabrilovich. Journal of Immunology, 2009

789 citations recorded by the source corpus.

Myeloid-derived suppressor cells (MDSC) are a major component of the immune suppressive network described in cancer and many other pathological conditions. Recent studies have demonstrated that one of the major mechanisms of MDSC-induced immune suppression is mediated by reactive oxygen species (ROS). However, the mechanism of this phenomenon remained unknown. In this study, we observed a substantial up-regulation of ROS by MDSC in all of seven different tumor models and in patients with head and neck cancer. The increased ROS production by MDSC is mediated by up-regulated activity of NADPH oxidase (NOX2). MDSC from tumor-bearing mice had significantly higher expression of NOX2 subunits, primarily p47phox and gp91phox, compared with immature myeloid cells from tumor-free mice. Expression of NOX2 subunits in MDSC was controlled by the STAT3 transcription factor. In the absence of NOX2 activity, MDSC lost the ability to suppress T cell responses and quickly differentiated into mature macrophages and dendritic cells. These findings expand our fundamental understanding of the biology of MDSC and may also open new opportunities for therapeutic regulation of these cells in cancer.

Subfields: Immunology, Neurology

View Paper: https://www.semanticscholar.org/paper/f951e41a45a54d9ba56e42f69d89ed09fcf528a4

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. D. Gabrilovich
2. T. Condamine
3. Je-in Youn
4. Cesar A. Corzo
5. P. Cheng
6. V. Bronte
7. Q. Guan
8. J. Massagué

In Neurology

1. D. Gabrilovich
2. J. Massagué
3. E. Batlle

Citations in the corpus

• Molecular mechanisms regulating myeloid-derived suppressor cell differentiation and function (2010, background): “Stat3 activation is directly responsible for upregulating transcription of the Nox2 components p47phox and gp91phox, increasing ROS production by MDSCs in tumor-bearing mice [37].”
• Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression (2018, positive): “Activated T cells were reported to secrete IL-10, which induces PD-L1 expression on MDSCs in a STAT3-dependent manner.90 Furthermore, STAT3 activation could induce VEGF production in MDSCs, whereas STAT3 inhibition by the tyrosinekinase inhibitor sunitinib reduced tumour angiogenesis and MDSC expans”
• HIF-1α regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment (2010, background): “As was reported previously (Corzo et al., 2009), spleen MDSC contain a high level of ROS and a relatively modest level of NO and arginase I activity (although it was still elevated in comparison with Gr-1+CD11b+ cells from naive mice).”