| First Author | Alhakeem SS | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 12 | Pages | 4180-4189 |
| PubMed ID | 29712773 | Mgi Jnum | J:263309 |
| Mgi Id | MGI:6164068 | Doi | 10.4049/jimmunol.1800241 |
| Citation | Alhakeem SS, et al. (2018) Chronic Lymphocytic Leukemia-Derived IL-10 Suppresses Antitumor Immunity. J Immunol 200(12):4180-4189 |
| abstractText | Chronic lymphocytic leukemia (CLL) patients progressively develop an immunosuppressive state. CLL patients have more plasma IL-10, an anti-inflammatory cytokine, than healthy controls. In vitro human CLL cells produce IL-10 in response to BCR cross-linking. We used the transgenic Emu-T cell leukemia oncogene-1 (TCL1) mouse CLL model to study the role of IL-10 in CLL associated immunosuppression. Emu-TCL mice spontaneously develop CLL because of a B cell-specific expression of the oncogene, TCL1. Emu-TCL1 mouse CLL cells constitutively produce IL-10, which is further enhanced by BCR cross-linking, CLL-derived IL-10 did not directly affect survival of murine or human CLL cells in vitro. We tested the hypothesis that the CLL-derived IL-10 has a critical role in CLL disease in part by suppressing the host immune response to the CLL cells. In IL-10R(-/-) mice, wherein the host immune cells are unresponsive to IL-10-mediated suppressive effects, there was a significant reduction in CLL cell growth compared with wild type mice. IL-10 reduced the generation of effector CD4 and CD8 T cells. We also found that activation of BCR signaling regulated the production of IL-10 by both murine and human CLL cells. We identified the transcription factor, Sp1, as a novel regulator of IL-10 production by CLL cells and that it is regulated by BCR signaling via the Syk/MAPK pathway. Our results suggest that incorporation of IL-10 blocking agents may enhance current therapeutic regimens for CLL by potentiating host antitumor immune response. |
