biostudies-literature00520Llao-Cid LDeutsche ForschungsgemeinschaftJosé Carreras Leukämie-StiftungDKFZ Clinician Scientist Program, supported by the Dieter Morszeck Foundation3152-3162https://www.ebi.ac.uk/biostudies/studies/S-EPMC8550953biostudies-literatureUnknown35(11)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 Eµ-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.LeukemiaEOMES is essential for antitumor activity of CD8⁺ T cells in chronic lymphocytic leukemia.PMC855095313R/2018SFB1074 subproject B1Hanna BSeiffert MBordas MChapaprieta VRoider TColomer DRoessner PMMartin-Subero JIOzturk SLlao-Cid LDietrich SIzcue AStilgenbauer S52falseEOMES is essential for antitumor activity of CD8⁺ T cells in chronic lymphocytic leukemia.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 Eµ-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.2021-01-01T00:00:00Z2021 Nov2024-11-06T02:30:36.387Z2022-02-11T12:44:02.951ZS-EPMC85509533373184810.1038/s41375-021-01198-1