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Increased expression of adenosine A3 receptor in tumor-infiltrating natural killer cells

Cellular & Molecular Immunology volume 18, pages 496–497 (2021)Cite this article

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Checkpoint blockade on lymphocyte surfaces has revolutionized cancer treatment. In particular, blockade of programmed cell death protein-1 by therapeutic antibodies is remarkably effective to reactivate T cells for the treatment of several cancer types.1,2 Immune checkpoint inhibitors that promote natural killer (NK) cell effector function have also recently demonstrated significant efficacy.3,4 Notably however, one of the main challenges of these clinical immunotherapies is that the majority of patients are resistant to immune checkpoint inhibitors.5 One practical approach to address this is identifying novel molecular targets and manipulating them to enhance antitumor immunity.

Adenosine is evidently a critical immunosuppressive metabolite that can limit the antitumor effects of cytotoxic lymphocytes.6 Aspects of the tumor microenvironment such as hypoxia and extracellular pressure effectively induce ATP conversion to adenosine by ectonucleotidase CD73 and CD39. Adenosine transmits inhibitory signals by activating adenosine receptor family molecules.7 In the current study the gene expression profiles of tumor-infiltrating NK cells from hepatocellular carcinoma (HCC) patients were analyzed using SMART-seq2 data (EGAS00001003449).8 Greater expression of adenosine A3 receptor (A3AR, also known as ADORA3) was detected in tumor-infiltrating NK cells than in peripheral NK cells (Supplementary Fig. 1A–C).

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Acknowledgements

This work was supported by the National Key R&D Program of China (2020YFA0710802) and the Natural Science Foundation of China (reference number 81872318, 82071768).

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Authors and Affiliations

  1. CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

    Jiacheng Bi & Chaoyue Zheng

  2. Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, 230027, Hefei, China

    Xiaohu Zheng

  3. Institute of Immunology, University of Science and Technology of China, 230027, Hefei, China

    Xiaohu Zheng

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  1. Jiacheng Bi
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Correspondence to Xiaohu Zheng.

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Bi, J., Zheng, C. & Zheng, X. Increased expression of adenosine A3 receptor in tumor-infiltrating natural killer cells. Cell Mol Immunol 18, 496–497 (2021). https://doi.org/10.1038/s41423-020-00632-1

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