| First Author | Llaó-Cid L | Year | 2021 |
| Journal | Leukemia | Volume | 35 |
| Issue | 11 | Pages | 3152-3162 |
| PubMed ID | 33731848 | Mgi Jnum | J:312354 |
| Mgi Id | MGI:6784155 | Doi | 10.1038/s41375-021-01198-1 |
| Citation | Llao-Cid L, et al. (2021) EOMES is essential for antitumor activity of CD8(+) T cells in chronic lymphocytic leukemia. Leukemia 35(11):3152-3162 |
| abstractText | Genome-wide association studies identified a single-nucleotide polymorphism (SNP) affecting the transcription factor Eomesodermin (EOMES) associated with a significantly increased risk to develop chronic lymphocytic leukemia (CLL). Epigenetic analyses, RNA sequencing, and flow cytometry revealed that EOMES is not expressed in CLL cells, but in CD8(+) T cells for which EOMES is a known master regulator. We thus hypothesized that the increased CLL risk associated with the EOMES SNP might be explained by its negative impact on CD8(+) T-cell-mediated immune control of CLL. Flow cytometry analyses revealed a higher EOMES expression in CD8(+) T cells of CLL patients compared to healthy individuals, and an accumulation of PD-1(+) EOMES(+) CD8(+) T cells in lymph nodes rather than blood or bone marrow in CLL. This was in line with an observed expansion of EOMES(+) CD8(+) T cells in the spleen of leukemic Emicro-TCL1 mice. As EOMES expression was highest in CD8(+) T cells that express inhibitory receptors, an involvement of EOMES in T-cell exhaustion and dysfunction seems likely. Interestingly, Eomes-deficiency in CD8(+) T cells resulted in their impaired expansion associated with decreased CLL control in mice. Overall, these observations suggest that EOMES is essential for CD8(+) T-cell expansion and/or maintenance, and therefore involved in adaptive immune control of CLL. |
