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Increased TIGIT expressing NK cells with dysfunctional phenotype in AML patients correlated with poor prognosis

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Abstract

AML is the most common blood cancer in adults with a high relapse and an overall poor survival rate. NK cells have been demonstrated to have the capacity to eradicate AML blast, and an impaired NK cell function is involved in AML development and progression. Immune checkpoints are involved in immune escape in various cancers. Immune checkpoints blockade therapy mainly aimed to unleash CD8+T cells function, but NK cells have emerged as new target. However, immune checkpoints profile on NK cells has not been observed in AML patients. Here, we studied the immune checkpoints expression of NK cells from AML patients at initial diagnosis and found increased PD-1, TIGIT and TIM-3 expression compared to NK cells from healthy donors. Further analysis showed that TIGIT expressing NK cells from AML patients had a dysfunctional phenotype, as TIGIT+NK cells exhibit lower antileukemia effect, cytokine production and degranulation compared to TIGIT−NK cells. TIGIT blockade could significantly enhance the function of NK cells. Moreover, AML patients with high frequency of TIGIT+NK cells had higher frequency of poor prognosis risk. Further analysis found that IL-10 upregulated TIGIT expression on NK cells. Thus, TIGIT blockade alone or in combination with other therapy might be potential strategy to treat AML.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81971482, to ES), the Science and Technology Program of Guangzhou (No.007095050049 to ES), and the Science and Technology Planned Project of Bureau of Education of Guangzhou (No. 1201610221, to ES).

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Author notes

  1. Guanfang Liu, Qi Zhang and Jingying Yang contributed equally to this work.

Authors and Affiliations

  1. The Second Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology; Sino-French Hoffmann Institute, School of Basic Sciences, Guangzhou Medical University, Guangzhou, China

    Guanfang Liu, Qi Zhang, Jingying Yang, Xiaomin Li, Juan Cheng & Erxia Shen

  2. Guangdong second provincial general Hospital, Guangzhou, China

    Guanfang Liu

  3. Department of Clinical Laboratory, Zhuhai Center for maternal and child Health care, Zhuhai, China

    Jingying Yang

  4. Department of Laboratory Medicine, Guangdong General Hospital, Academy of Medical Sciences, Guangzhou, China

    Luhua Xian, Wenmin Li, Ting Lin & Maohua Zhou

  5. Guangzhou Blood Center, Guangzhou, China

    Qiwen Lin & Xiuzhang Xu

  6. Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, US

    Qin Li

  7. Shenzhen Withsum Technology Limited, Shenzhen, China

    Yu Lin

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Contributions

ES, MZ and GL conceived the experiments. GL, ZQ and JY performed the study. ES, GL and ZQ analyzed the data. XL, JC, and QL assisted to perform the experiments. YL assisted to do the statistical analysis. LX, WL, TL, QL and XX collected the samples. ES and GL wrote the paper. All authors contributed to the manuscript review. All authors contributed to the article and approved the submitted version.

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Correspondence to Maohua Zhou or Erxia Shen.

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Conflict of interest

YL was employed by Shenzhen Withsum Technology Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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This study was conducted in compliance with the Declaration of Helsinki and was approved by the ethics committee of Guangdong General Hospital (Guangzhou, China).

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Erxia Shen is the first corresponding author.

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Liu, G., Zhang, Q., Yang, J. et al. Increased TIGIT expressing NK cells with dysfunctional phenotype in AML patients correlated with poor prognosis. Cancer Immunol Immunother 71, 277–287 (2022). https://doi.org/10.1007/s00262-021-02978-5

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