期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 50, 期 12, 页码 2055-2066出版社
WILEY
DOI: 10.1002/eji.202048626
关键词
CD73; head and neck cancer; T cells
类别
资金
- Immune Function Core Laboratory in the Center for AIDS Research (NIH) [AI036219]
Recent studies have implicated a role for adenosine-dependent immunosuppression in head and neck tumor microenvironments. We describe expression of CD73, an enzyme critical to the generation of adenosine from extracellular AMP, in T cells and other cell types within human head and neck tumors. Flow cytometric analyses of tumor-infiltrating cells indicate that CD3(+)cells are the predominant source of CD73 among immune infiltrating cells and that CD73 expression, especially among CD8(+)T cells, is inversely related to indices of T cell infiltration and T cell activation in the microenvironment of head and neck tumors. We provide evidence that CD73 expression on peripheral T cells and levels of soluble CD73 in circulation are correlated with CD73 expression on CD8(+)T cells in tumors. Moreover, fluorescent microscopy studies reveal that CD8(+)CD73(+)cells are observed in close proximity to tumor cells as well as in surrounding tissue. In vitro studies with peripheral blood T cells indicate that anti-CD3-stimulation causes loss of CD73 expression, especially among cells that undergo proliferation and that exogenous AMP can impair T cell proliferation, while sustaining CD73 expression. These data suggest that CD8(+)CD73(+)T cells may be especially important mediators of immunosuppression in human head and neck cancer.
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