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CD277 agonist enhances the immunogenicity of relapsed/refractory acute myeloid leukemia towards Vδ2+ T cell cytotoxicity

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Abstract

Relapse and refractoriness remain the major obstacles in clinical treatment of acute myeloid leukemia (AML). Efficacy of current therapeutic strategies for relapsed/refractory (R/R) AML is generally unsatisfying. Vδ2+ T cells have become an attractive candidate for immunotherapy of various types of tumors. However, the results were not exciting in some pilot studies utilizing Vδ2 cell-based protocols to treat R/R AML. Functional receptors on Vδ2 cells and immunogenic ligands on leukemia cells are both critical to the anti-AML effect of Vδ2 cells, which have not been characterized in the context of R/R AML. CD277 can bind to phosphoantigens and promote the activation of Vδ2 cells. Anti-CD277 (clone 20.1) monoclonal antibody (20.1 mAb) has been identified as an agonist of CD277. Whether 20.1 mAb sensitizes R/R AML cells awaits investigation. Herein, we showed that the expressions of activating receptors on Vδ2 cells and CD277 on leukemia cells were deficient in patients with R/R AML. While agonists for NKG2D and TRAIL ligands did not increase the immunogenicity of R/R AML cells, 20.1 mAb significantly enhanced the cytotoxicity of Vδ2 cells on the drug-resistant human AML cell line and different types of primary AML cells from R/R patients. The sensitizing effect of 20.1 mAb was dependent on inducing degranulation of Vδ2 cells. These findings suggest a decisive role of CD277 in mediating the recognition of R/R AML cells by Vδ2+ T cells. CD277 agonist combining adoptive transfer of Vδ2+ T cells may improve the efficacy in the treatment of R/R AML.

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Funding

This study is supported by the National Natural Science Foundation of China (No. 81770191).

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Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, 11 Xizhimen South Street, Beijing, 100044, China

    Tianhui Dong, Ning Wu, Haitao Gao, Shuang Liang, Xinyu Dong, Ting Zhao, Qian Jiang & Jiangying Liu

  2. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China

    Shuang Liang

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  1. Tianhui Dong
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Correspondence to Jiangying Liu.

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All procedures were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. The study protocols have been approved by the Ethical Committee of Peking University Institute of Hematology. All patients signed the consent forms.

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Dong, T., Wu, N., Gao, H. et al. CD277 agonist enhances the immunogenicity of relapsed/refractory acute myeloid leukemia towards Vδ2+ T cell cytotoxicity. Ann Hematol 101, 2195–2208 (2022). https://doi.org/10.1007/s00277-022-04930-8

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  • DOI: https://doi.org/10.1007/s00277-022-04930-8

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