| First Author | Zhao X | Year | 2012 |
| Journal | J Clin Invest | Volume | 122 |
| Issue | 11 | Pages | 4094-104 |
| PubMed ID | 23064360 | Mgi Jnum | J:193549 |
| Mgi Id | MGI:5468754 | Doi | 10.1172/JCI64115 |
| Citation | Zhao X, et al. (2012) TNF signaling drives myeloid-derived suppressor cell accumulation. J Clin Invest 122(11):4094-104 |
| abstractText | TNF, an inflammatory cytokine that is enriched in the tumor microenvironment, promotes tumor growth and subverts innate immune responses to cancer cells. We previously reported that tumors implanted in TNF receptor-deficient (Tnfr-/-) mice are spontaneously rejected; however, the molecular mechanisms underlying this rejection are unclear. Here we report that TNF signaling drives the peripheral accumulation of myeloid-derived suppressor cells (MDSCs). MDSCs expand extensively during inflammation and tumor progression in mice and humans and can enhance tumor growth by repressing T cell-mediated antitumor responses. Peripheral accumulation of MDSCs was drastically impaired in Tnfr-/- mice. Signaling of TNFR-2, but not TNFR-1, promoted MDSC survival through upregulation of cellular FLICE-inhibitory protein (c-FLIP) and inhibition of caspase-8 activity. Loss of TNFRs impaired the induction of MDSCs from bone marrow cells, but this could be reversed by treatment with caspase inhibitors. These results demonstrate that TNFR-2 signaling promotes MDSC survival and accumulation and helps tumor cells evade the immune system. |
