Effects of Inflammatory Factors on Mesenchymal Stem Cells and Their Role in the Promotion of Tumor Angiogenesis in Colon Cancer

Liu, Yan; Han, Zhipeng; Zhang, Shanshan; Jing, Yingying; Bu, Xinxin; Wang, Chenyang; Sun, Kai; Jiang, Guocheng; Zhao, Xue; Li, Rong; Gao, Lu; Zhao, Qinqin; Wu, Mengchao; Wei, Lixin

doi:10.1074/jbc.m110.213108

Cited by 166 publications

(131 citation statements)

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“…Similarly, the interaction of MSCs with lung cancer cell lines was found to cause stanniocalcin-1 (STC-1) secretion by the activated MSCs, which in turn upregulates uncoupling protein 2 to protect the neighboring cancer cells from ROS-induced apoptosis. 130,131 Taken together, these findings raise the notion that contextual signals control the manner of MSC activation and, accordingly, may regulate their functions within the tumor microenvironment (discussed in more detail below).…”

Section: Mscs In Tumor Pathogenesismentioning

confidence: 91%

Mesenchymal stem cells in tumor development

Cuiffo¹,

Karnoub²

2012

Cell Adhesion & Migration

166

120

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Section: Mscs In Tumor Pathogenesismentioning

confidence: 91%

Mesenchymal stem cells in tumor development

Cuiffo¹,

Karnoub²

2012

Cell Adhesion & Migration

166

120

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“…The important insight in the present study is that licensed MSCs deploy complementary and nonoverlapping T cell veto mechanisms, namely, IDO and B7H1/B7DC upregulation. These observations may inform a strategy targeting tumor microenvironment as part of a cancer immunotherapy strategy where contemporaneous PD1 and IDO blockade may be required for optimally overcoming immune escape mechanisms by tumor cloaked in host-derived stromal cells (59,60). Furthermore, these data inform the translational use of culture-expanded MSCs as a transfusion product to treat autoimmune and alloimmune ailments (16).…”

Section: Discussionmentioning

confidence: 99%

IDO-Independent Suppression of T Cell Effector Function by IFN-γ–Licensed Human Mesenchymal Stromal Cells

Chinnadurai

Copland

Patel

et al. 2014

The Journal of Immunology

223

214

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Human bone marrow–derived mesenchymal stromal cells (MSCs) inhibit proliferation of activated T cells, and IFN-γ plays an important role in this process. This IFN-γ–licensed veto property is IDO-dependent. To further decipher the mechanistic underpinnings of MSC veto function on T cells, we investigated the effect of MSCs and IFN-γ–licensed MSCs on T cell effector function as assayed by cytokine secretion of T cells. Although MSCs and IFN-γ–licensed MSCs inhibit T cell proliferation, only IFN-γ–licensed MSCs significantly inhibit Th1 cytokine (IFN-γ, TNF-α, and IL-2) production by T cells. Additionally, IFN-γ–licensed MSCs inhibit T cell degranulation as well as single, double, and triple cytokine–producing T cells. Although IFN-γ–licensed MSCs upregulate their IDO activity, we found that MSC IDO catalytic function is dispensable with regard to MSC-driven inhibition of T cell effector function. Novel flow cytometry based functional screening of MSC-expressed, IFN-γ–licensed inhibitory molecules identified B7H1 and B7DC/PD1 pathways as essential effectors in blocking T cell function. Small interfering RNA–mediated blocking of B7H1 and B7DC reverses the inhibitory potential of IFN-γ–licensed MSCs on T cell effector function. Mechanistic analysis revealed that clustering of MHC and coinhibitory molecules are indispensable for the inhibitory effect of IFN-γ MSCs. Although exogenous IL-2 reverses B7H1-Ig–mediated inhibition of T cell proliferation, it does not affect the veto function of IFN-γ MSCs on both T cell proliferation and effector function. Our results reveal a new immunosuppressive property of IFN-γ–licensed MSCs that inhibits T cell effector function independent of IDO but through the ligands for PD1.

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“…MSCs are nonhematopoietic, multipotent cells which are known to be actively recruited to the site of tumours, including colorectal tumours and their metastases [5,6,7]. Despite this, our knowledge of colon cancer cell-MSC interactions remains limited, and the role of MSCs within colon tumours has yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%