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CD226: a potent driver of antitumor immunity that needs to be maintained

Cellular & Molecular Immunology volume 19, pages 969–970 (2022)Cite this article

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CD226 (DNAX Accessory Molecule-1, DNAM-1, PTA-1, TLiSA1) is a transmembrane protein that is expressed on T cells, natural killer (NK) cells, B cells, monocytes, and platelets. CD226, together with the inhibitory receptors TIGIT and CD96, belongs to a cell-surface receptor family3 that binds nectin and nectin-like proteins. The interesting feature of this family is that these receptors compete for common ligands. For example, CD226 competes with TIGIT and CD96 for binding to CD155 (Nectin-like molecule 5, Necl-5, PVR) and CD112 (Nectin-2), and the expression of these ligands is usually abundant in tumors.

CD226 has been shown to be required for optimal immunosurveillance in various tumor models. Recently, Weulersse et al.1 and Braun et al.2 further revealed the essential role of CD226 in facilitating the antitumor immune response. These groups showed that the absence of CD226 limits LFA-1 activation and indicates hyporesponsive CD8+ T cells. During tumor development, CD226−CD8+ T cells accumulate in tumors and correlate with poor survival in tumor patients. Increased CD226 expression on tumor-infiltrating CD8+ T cells correlates with increased effector functions by these cells in mouse tumor models and in head and neck squamous cell carcinoma patients. The researchers also showed that the absence of CD226 limits the efficacy of anti-PD1 checkpoint blockade both in the B16K1 melanoma model and the MC38 colon cancer model. Importantly, CD226 levels in melanoma tumor samples from patients were assessed before PD1-based immune checkpoint blockade therapy and positively correlated with patient survival in both the discovery and validation cohorts, independent of the levels of CD8+ T cell infiltration in tumors. These data demonstrate that CD226 is a potent driver of antitumor immunity.

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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 82071768).

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  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

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Bi, J. CD226: a potent driver of antitumor immunity that needs to be maintained. Cell Mol Immunol 19, 969–970 (2022). https://doi.org/10.1038/s41423-020-00633-0

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