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

Lepletier, Ailin, Lutzky, Viviana P., Mittal, Deepak, Stannard, Kimberley, Watkins, Thomas, Ratnatunga, Champa N., Smith, Corey, McGuire, Helen M., Kemp, Roslyn A., Mukhopadhyay, Pamela, Waddell, Nicola, Smyth, Mark J., Dougall, William C., and Miles, John J. (2018) The immune checkpoint CD96 defines a distinct lymphocyte phenotype and is highly expressed on tumor-infiltrating T cells. Immunology and Cell Biology. (In Press)

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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.

Item ID: 56688
Item Type: Article (Research - C1)
ISSN: 1440-1711
Keywords: CD96, checkpoint blockade, T cells, tumor-infiltrating T cells
Copyright Information: © 2018 Australasian Society for Immunology Inc.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC Development Grant 1093566, NHMRC Senior Principal Research Fellowship 1078671, NHMRC Career Development Fellowship 1131732
Date Deposited: 11 Feb 2019 23:38
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 100%
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