| First Author | Rehm A | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 4 | Pages | 1020-33 |
| PubMed ID | 21586747 | Mgi Jnum | J:174881 |
| Mgi Id | MGI:5141366 | Doi | 10.1182/blood-2010-11-321265 |
| Citation | Rehm A, et al. (2011) Cooperative function of CCR7 and lymphotoxin in the formation of a lymphoma-permissive niche within murine secondary lymphoid organs. Blood 118(4):1020-33 |
| abstractText | Lymphoma cell survival and progression are putatively dependent on a specific microanatomic localization within secondary lymphoid organs. Despite compelling data correlating homeostatic chemokine receptor expression and human lymphoma pathogenesis, genetic models that either mimic lymphoma dissemination or dissect a crosstalk of lymphoma and stromal cells are missing. Applying the genetically tractable Emu-Myc transgenic mouse model, we show that the chemokine receptor CCR7 regulates Emu-Myc lymphoma homing to lymph nodes and distinctive microanatomic sites of the spleen. CCR7-controlled access of lymphoma cells to the splenic T-cell zone led to a significant survival advantage compared with CCR7-deficient lymphoma cells, which were excluded from this zone. Within the niche, lymphoma cells stimulated a reciprocal cross-talk with gp38(+) fibroblastic reticular cells. This reciprocal cooperation program was mediated by lymphoma B cell-presented lymphotoxin, which acted on lymphotoxin-beta-receptor-bearing stromal cells followed by alteration of stromal cellular composition. Cross-talk inhibition by lymphotoxin-alpha deletion and using a lymphotoxin-beta receptor-immunoglobulin fusion protein impaired lymphoma growth. Thus, abrogation of CCR7-governed migration and of sustained lymphotoxin signaling could provide new targets in lymphoma therapy. |
