| First Author | Lewinsky H | Year | 2018 |
| Journal | J Clin Invest | Volume | 128 |
| Issue | 12 | Pages | 5465-5478 |
| PubMed ID | 30277471 | Mgi Jnum | J:271474 |
| Mgi Id | MGI:6279733 | Doi | 10.1172/JCI96610 |
| Citation | Lewinsky H, et al. (2018) CD84 regulates PD-1/PD-L1 expression and function in chronic lymphocytic leukemia. J Clin Invest 128(12):5465-5478 |
| abstractText | Chronic lymphocytic leukemia (CLL) is characterized by clonal proliferation and progressive accumulation of mature B lymphocytes in the peripheral blood, lymphoid tissues, and bone marrow. CLL is characterized by profound immune defects leading to severe infectious complications. T cells are numerically, phenotypically, and functionally highly abnormal in CLL, with only limited ability to exert antitumor immune responses. Exhaustion of T cells has also been suggested to play an important role in antitumor responses. CLL-mediated T cell exhaustion is achieved by the aberrant expression of several inhibitory molecules on CLL cells and their microenvironment, prominently the programmed cell death ligand 1/programmed cell death 1 (PD-L1/PD-1) receptors. Previously, we showed that CD84, a member of the SLAM family of receptors, bridges between CLL cells and their microenvironment. In the current study, we followed CD84 regulation of T cell function. We showed that cell-cell interaction mediated through human and mouse CD84 upregulates PD-L1 expression on CLL cells and in their microenvironment and PD-1 expression on T cells. This resulted in suppression of T cell responses and activity in vitro and in vivo. Thus, our results demonstrate a role for CD84 in the regulation of immune checkpoints by leukemia cells and identify CD84 blockade as a therapeutic strategy to reverse tumor-induced immune suppression. |
