The immune checkpoint CD96 defines a distinct lymphocyte phenotype and is highly expressed on tumor-infiltrating T cells

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Abstract

CD96 has recently been shown to be a potent immune checkpoint molecule in mice, but a similar role in humans is not known. In this study, we provide a detailed map of CD96 expression across human lymphocyte lineages, the kinetics of CD96 regulation on T-cell activation and co-expression with other conventional and emerging immune checkpoint molecules. We show that CD96 is predominantly expressed by T cells and has a unique lymphocyte expression profile. CD96high T cells exhibited distinct effector functions on activation. Of note, CD96 expression was highly correlated with T-cell markers in primary and metastatic human tumors and was elevated on antigen-experienced T cells and tumor-infiltrating lymphocytes. Collectively, these data demonstrate that CD96 may be a promising immune checkpoint to enhance T-cell function against human cancer and infectious disease.

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Lepletier, A., Lutzky, V. P., Mittal, D., Stannard, K., Watkins, T. S., Ratnatunga, C. N., … Miles, J. J. (2019). The immune checkpoint CD96 defines a distinct lymphocyte phenotype and is highly expressed on tumor-infiltrating T cells. Immunology and Cell Biology, 97(2), 152–164. https://doi.org/10.1111/imcb.12205

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