| First Author | Ku AW | Year | 2016 |
| Journal | Elife | Volume | 5 |
| PubMed ID | 27929373 | Mgi Jnum | J:269688 |
| Mgi Id | MGI:6204218 | Doi | 10.7554/eLife.17375 |
| Citation | Ku AW, et al. (2016) Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes. Elife 5:e17375 |
| abstractText | Myeloid-derived suppressor cells (MDSC) contribute to an immunosuppressive network that drives cancer escape by disabling T cell adaptive immunity. The prevailing view is that MDSC-mediated immunosuppression is restricted to tissues where MDSC co-mingle with T cells. Here we show that splenic or, unexpectedly, blood-borne MDSC execute far-reaching immune suppression by reducing expression of the L-selectin lymph node (LN) homing receptor on naive T and B cells. MDSC-induced L-selectin loss occurs through a contact-dependent, post-transcriptional mechanism that is independent of the major L-selectin sheddase, ADAM17, but results in significant elevation of circulating L-selectin in tumor-bearing mice. Even moderate deficits in L-selectin expression disrupt T cell trafficking to distant LN. Furthermore, T cells preconditioned by MDSC have diminished responses to subsequent antigen exposure, which in conjunction with reduced trafficking, severely restricts antigen-driven expansion in widely-dispersed LN. These results establish novel mechanisms for MDSC-mediated immunosuppression that have unanticipated implications for systemic cancer immunity. |
