Exploring NK cell receptor dynamics in paediatric leukaemias: implications for immunotherapy and prognosis

探索儿童白血病中的 NK 细胞受体动态:对免疫治疗和预后的影响

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作者:Cui Tu, Irina Buckle, Ingrid Leal Rojas, Gustavo Rodrigues Rossi, David P Sester, Andrew S Moore, Kristen Radford, Camille Guillerey, Fernando Souza-Fonseca-Guimaraes

Conclusion

We provide an in-depth analysis of NK cell populations in paediatric leukaemia patients. These results support the development of immunotherapies targeting immunosuppressive receptors, such as NKG2A, to enhance innate immunity against paediatric leukaemia.

Methods

In this study, we conducted a high-dimensional examination of the cell surface expression of 16 NK cell receptors in paediatric patients with acute myeloid leukaemia and acute lymphoblastic leukaemia, as well as in samples of non-age matched adult peripheral blood (APB) and umbilical cord blood (UCB). An unsupervised analysis was carried out in order to identify NK cell populations present in paediatric leukaemias.

Results

We observed that leukaemia NK cells clustered together with UCB NK cells and expressed relatively higher levels of the NKG2A receptor compared to APB NK cells. In addition, CD56dimCD16+CD57- NK cells lacking NKG2A expression were mainly absent in paediatric leukaemia patients. However, CD56br NK cell populations expressing high levels of NKG2A were highly represented in paediatric leukaemia patients. NKG2A expression on leukaemia NK cells was found to be positively correlated with the expression of its ligand, suggesting that the NKG2A-HLA-E interaction may play a role in modifying NK cell responses to leukaemia cells.

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