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Eomesodermin: A Master Regulator of CD8-Positive T Cells in CLL?

By: Vanessa A. Carter, BS
Posted: Wednesday, May 5, 2021

A single-nucleotide polymorphism in the transcription factor eomesodermin may be associated with an increased risk of chronic lymphocytic leukemia (CLL). Martina Seiffert, PhD, of the German Cancer Research Center, Heidelberg, and colleagues hypothesized that this risk might be defined by the negative impact on CD8-positive T-cell–mediated immune control of CLL. Published in the journal Leukemia, their results showed that eomesodermin is necessary for CD8-positive T-cell expansion and may be involved in adaptive immune control.

The chromatin status and RNA expression of the eomesodermin locus were analyzed in B cells and T cells at various differentiation states. There was active chromatin in T cells and natural killer cells, with CD8-positive memory T cells displaying the most activity; the mean percentage of eomesodermin-positive, CD8-positive T cells was 61.5 ± 8.39%. In contrast, there was no eomesodermin expression in CLL cells.

Samples were compared with age-matched healthy donors to discover any abnormalities. A significantly higher expression of eomesodermin-positive, CD8-positive T-effector, and T-effector memory cells was found in patients with CLL versus healthy donors. Additionally, eomesodermin-positive PD-1–positive cells were discovered in significantly higher numbers in lymph nodes compared with peripheral blood.

An Eµ-TCL1 mouse model of CLL was used to examine the role of these eomesodermin-expressing CD8-positive T cells. A larger proportion of CD8-positive T cells expressed eomesodermin in these mice compared with sex- and age-matched wild-type mice. The number of CD8-positive T cells and eomesodermin-positive CD8-positive T cells was positively associated with disease load and the presence of inhibitory receptors.

Eomesodermin-negative/negative bone marrow chimeric mice were generated to analyze T-cell–mediated control of CLL. These mice displayed a lower total number of CD8-positive T cells, likely explaining the enhanced tumor development due to diminished control. Of note, the lack of eomesodermin was attributed to a larger number of CD8-positive T cells expressing PD-1 but not LAG3.

Disclosure: The study authors reported no conflicts of interest.



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