Higher frequency of peripheral blood CD103 + CD8 + T cells with lower levels of PD-1 and TIGIT expression related to favorable outcomes in leukemia patients

Leukemia is a prevalent pediatric life-threatening hematologic malignancy with a poor prognosis. Targeting immune checkpoints (ICs) to reverse T cell exhaustion is a potentially effective treatment for leukemia. Tissue resident memory T (T ) cells have been found to predict the efficacy of programme...

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Veröffentlicht in:Frontiers in immunology 2024-09, Vol.15, p.1437726
Hauptverfasser: Liu, Lian, Lai, Wenpu, Zhuo, Xiaoling, Chen, Sihui, Luo, Xiaodan, Tan, Huo
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Sprache:eng
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Zusammenfassung:Leukemia is a prevalent pediatric life-threatening hematologic malignancy with a poor prognosis. Targeting immune checkpoints (ICs) to reverse T cell exhaustion is a potentially effective treatment for leukemia. Tissue resident memory T (T ) cells have been found to predict the efficacy of programmed death receptor-1 inhibitor (anti-PD-1) therapy in solid tumors. However, the IC characteristics of T cells in leukemia and their relationship with prognosis remain unclear. We employed multi-color flow cytometry to evaluate the frequencies of CD103 CD4 and CD103 CD8 T cells in the peripheral blood (PB) of patients with acute myeloid leukemia and B-cell acute lymphoblastic leukemia compared to healthy individuals. We examined the expression patterns of PD-1 and T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) within the circulating CD103 T cell subsets affected by leukemia. To further elucidate the immunological landscape, we assessed the differentiation status of CD103 T cells across various disease states in patients with leukemia. Our findings showed a significant increase in the frequency of CD103 CD8 T cells in the PB of patients with leukemia who had achieved complete remission (CR) compared to those in the and relapsed/refractory (RR) stages. This increase was accompanied by a notable decrease in the expression levels of PD-1 and TIGIT in CD103 CD8 T cells in the CR stage. Additionally, our analysis revealed a higher proportion of CD103 CD8 T cells in the central memory (TCM) and effector memory (TEM) subsets of the immune profile. Notably, the proportions of CD103 naïve T cells, CD103 TEM, and CD103 terminally differentiated T cells within the CD8 T cell population were significantly elevated in patients with CR compared to those in the /RR stages. The data indicate that circulating higher frequency of CD103 CD8 T cells with lower expression of PD-1 and TIGIT are associated with favorable outcomes in patients with leukemia. This suggests a potential role of T cells in leukemia prognosis and provides a foundation for developing targeted immunotherapies.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2024.1437726