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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1437726
This article is part of the Research Topic Ubiquitination in Tumor Pathogenesis and Progression and its Therapeutic Potential View all articles
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
Provisionally accepted- 1 Guangzhou Medical University, Guangzhou, China
- 2 Department of Hematology, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
- 3 Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China
- 4 Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China
- 5 Department of Systems Biomedical Sciences, School of Medicine, Jinan University, Guangzhou, China
- 6 Flow Morphology Group, Special Testing Technology Center, Guangzhou Huayin Medical Testing Center Special Testing Technology Center, Guangzhou, China
Background: 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 (TRM) 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 TRM 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. Results: 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 de novo (DN) 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 + naï ve 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 DN/RR stages. Conclusion: 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 TRM cells in leukemia prognosis and provides a foundation for developing targeted immunotherapies.
Keywords: Leukemia, t cell exhaustion, immune checkpoints, Tissue resident memory T cells, CD103+CD8+ T cells, PD-1, TIGIT
Received: 24 May 2024; Accepted: 02 Sep 2024.
Copyright: © 2024 Liu, Lai, Zhuo, Chen, Luo and Tan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiaoling Zhuo, Flow Morphology Group, Special Testing Technology Center, Guangzhou Huayin Medical Testing Center Special Testing Technology Center, Guangzhou, China
Sihui Chen, Guangzhou Medical University, Guangzhou, China
Huo Tan, Guangzhou Medical University, Guangzhou, China
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