The Liver Is a Site for Tumor-Induced Myeloid-Derived Suppressor Cell Accumulation and Immunosuppression
Open Access
- 1 July 2009
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 69 (13), 5514-5521
- https://doi.org/10.1158/0008-5472.can-08-4625
Abstract
Tumor-induced immunosuppression plays a key role in tumor evasion of the immune system. A key cell population recognized as myeloid-derived suppressor cells (MDSC) contributes and helps orchestrate this immunosuppression. MDSC can interact with T cells, macrophages, and natural killer cells to create an environment favorable for tumor progression. In various tumor models, their presence at high levels has been reported in the bone marrow, blood, spleen, and tumor. We report for the first time that MDSC accumulate and home to the liver in addition to the other organs. Liver MDSC suppress T cells and accumulate to levels comparable with splenic MDSC. Additionally, hematopoiesis in the liver contributes to the dramatic expansion of MDSC in this organ. Furthermore, MDSC in the liver interact with macrophages, also known as Kupffer cells, and cause their up-regulation of PD-L1, a negative T-cell costimulatory molecule. The liver is thus an organ in which MDSC accumulate and can contribute to immunosuppression directly and indirectly. MDSC play a role in various pathologic states in addition to cancer, and these results contribute to our understanding of their biology and interactions with immune-related cells. [Cancer Res 2009;69(13):5514–21]Keywords
This publication has 47 references indexed in Scilit:
- Myeloid-derived suppressor cells as regulators of the immune systemNature Reviews Immunology, 2009
- A New Population of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma Patients Induces CD4+CD25+Foxp3+ T CellsGastroenterology, 2008
- Tumor-Induced Immune Suppression ofIn vivoEffector T-Cell Priming Is Mediated by the B7-H1/PD-1 Axis and Transforming Growth Factor βCancer Research, 2008
- Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapyCancer Immunology, Immunotherapy, 2008
- PD-1 and Its Ligands in Tolerance and ImmunityAnnual Review of Immunology, 2008
- Reversion of immune tolerance in advanced malignancy: modulation of myeloid-derived suppressor cell development by blockade of stem-cell factor functionBlood, 2008
- The mouse mammary carcinoma 4T1: characterization of the cellular landscape of primary tumours and metastatic tumour fociInternational Journal of Experimental Pathology, 2007
- MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T cell suppression and Th2 polarization in sepsisThe Journal of Experimental Medicine, 2007
- B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinomaThe Journal of Experimental Medicine, 2006
- The Three Es of Cancer ImmunoeditingAnnual Review of Immunology, 2004