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Direct interaction between CD155 and CD96 promotes immunosuppression in lung adenocarcinoma

Cellular & Molecular Immunology volume 18, pages 1575–1577 (2021)Cite this article

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Despite the advance in targeted therapy, lung adenocarcinoma (LUAD) remains one of the leading causes of death in patients with cancer. CD155, a member of poliovirus receptor–related (PRR) family, has been identified as the ligand of the Ig-like receptors tactile (CD96) and DNAM-1 (CD226) on T cells. The interaction of CD155 with CD96 transmits an inhibitory signal and suppresses immune response. The interaction of CD155 with CD226 enhances the immune response.1,2,3 CD155 expression has been shown to be elevated in many types of cancers4,5 and is involved with immune suppression in melanoma.6 However, how CD155/CD96 is involved in immune response in the tumor microenvironment of LUAD remains unknown.

CD96, as a co-inhibitory molecule, competes with the co-stimulatory molecule of CD226 for binding to CD155. The lost balance between these two molecules might lead to a hypo- or hyper-immune response. We found that CD8 T cells in PBMC from LUAD patients expressed higher levels of CD96 compared with HC. CD96 expression was even higher in TILs than in T cells from the circulation of LUAD patients (Fig. 1c, d). CD226 expression was substantially lower in CD8 T cells from PBMC of LUAD patients than that in HC. CD226 expression in TILs was further decreased compared with that from the circulation of LUAD patients (Fig. 1e, f). These data indicated that the imbalance of CD155/CD96 and CD155/CD226 signals in LUAD patients could lead to hypo-immune response.

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Acknowledgements

We thank all patients enrolled in this study.

Funding

This work was supported by grants from YFC (2017YFC1308800), National Natural Science Foundation of China to Zunfu Ke (30900650, 81372501, 81572260, 81773299, 81701834, 81502327, 81172232, and 31430030), and Guangdong Natural Science Foundation (2011B031800025, S2012010008378, S2012010008270, S2013010015327, 2013B021800126, 20090171120070, 9451008901002146, 2013B021800126, 2014A030313052, 2014J4100132, 2015A020214010, 2016A020215055, 201704020094, 2013B021800259, 2017B070705002, 16ykjc08, and 2015ykzd07).

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Author notes

  1. These authors contributed equally: Hui Zhang, Qianwen Liu, Yiyan Lei

Authors and Affiliations

  1. Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Hui Zhang & Zunfu Ke

  2. Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Hui Zhang

  3. Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510080, China

    Qianwen Liu

  4. Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Yiyan Lei

  5. Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Jianwen Zhou, Wenting Jiang, Yongmei Cui, Qiong He, Junfeng Zhu, Yu Sun & Zunfu Ke

  6. Department of Pathology, Longgang Central Hospital of Shenzhen, Affiliated Longgang Hospital of Zunyi Medical University, Shenzhen, 518116, China

    Zheng Zhu

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Contributions

Conception and design: ZK, HZ, and YC. Funding support: ZK. Collection and assembly of data: QL, YL, JZ, WJ, QH, JZ, ZZ, and YS. Data analysis and interpretation: ZK and HZ. Manuscript writing: ZK and HZ. Final approval of manuscript: All authors.

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Correspondence to Zunfu Ke.

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Zhang, H., Liu, Q., Lei, Y. et al. Direct interaction between CD155 and CD96 promotes immunosuppression in lung adenocarcinoma. Cell Mol Immunol 18, 1575–1577 (2021). https://doi.org/10.1038/s41423-020-00538-y

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