| Summary: | 碩士 === 國立臺灣大學 === 免疫學研究所 === 104 === Galectin-9, a tandem-repeat type galectin, was first identified in patients with a nodular sclerosis type of Hodgkin’s disease. Previous studies demonstrated various regulatory roles of galectin-9 in the immune responses. However, role of galectin-9 in cancer biology remains elusive. Here, we found galectin-9 expression in germinal centre B-cell-like diffuse large B cell lymphoma (GCB DLBCLs) was up-regulated amongst germinal center lymphomas. To determine the role of elevated galectin-9 expression in vivo, we used NOD/SCID xenograft model of GCB DLBCLs. Strikingly, we observed a dramatic reduction of tumor volume and weight in mice receiving galectin-9 knockdown GCB DLBCL cells. Interestingly, knockdown of galectin-9 did not affect the tumorigenicity in NOD scid gamma (NSG) xenograft model, which implied natural killer (NK) cells might be responsible for the reduced tumor size in NOD/SCID mice. Thus, depletion of NK cells was achieved by anti-asGM1 antibody in NOD/SCID mice. As a result, we found partially restored tumorigenicity in NOD/SCID mice engrafted with galectin-9 knockdown GCB DLBCLs after NK cell depletion. Moreover, tumor-infiltrating NK cells were significantly increased in galectin-9-depleted tumors in NOD/SCID mice. In term of molecular mechanisms, knockdown of galectin-9 induces neither apoptosis nor cell cycle arrest in GCB DLBCLs. On the other hand, we found that the level of c-Jun, a regulator in tumor microenvironment, was decreased in galectin-9 knockdown GCB DLBCL tumors. These data suggested that galectin-9 derived from GCB-DLBCL might cause the immune escape through inhibiting NK cell activity.
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