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.

中文翻译：

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头颈部癌患者的肿瘤微环境中的CD8 + CD73 + T细胞与肿瘤组织中T细胞浸润和激活减少有关。

最近的研究表明在头颈部肿瘤微环境中腺苷依赖的免疫抑制作用。我们描述了CD73的表达，一种对细胞外AMP产生腺苷至关重要的酶，在人类头颈部肿瘤的T细胞和其他细胞类型中表达。肿瘤浸润细胞的流式细胞仪分析表明，CD3 ⁺细胞是免疫浸润细胞中CD73的主要来源，并且CD73的表达，特别是CD8 ⁺ T细胞之间的表达，与T细胞浸润和T细胞活化指数呈负相关。头颈部肿瘤的微环境。我们提供的证据表明，外周血T细胞上的CD73表达和循环中可溶性CD73的水平与CD8 ⁺上的CD73表达相关肿瘤中的T细胞。此外，荧光显微镜研究表明，在靠近肿瘤细胞以及周围组织的地方观察到了CD8 ⁺ CD73 ⁺细胞。对外周血T细胞的体外研究表明，抗CD3刺激会导致CD73表达丧失，尤其是在经历增殖的细胞中，外源AMP会损害T细胞增殖，同时维持CD73表达。这些数据表明，CD8 ⁺ CD73 ⁺ T细胞可能是人头颈部癌症免疫抑制的特别重要的介质。