Background CD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Several CD73 inhibitors and adenosine receptor antagonists are being evaluated in phase I clinical trials. Patients and methods Full-face sections from formalin-fixed paraffin-embedded primary breast tumors from 122 samples of triple-negative breast cancer (TNBC) from the BIG 02-98 adjuvant phase III clinical trial were included in our analysis. Using multiplex immunofluorescence and image analysis, we assessed CD73 protein expression on tumor cells, tumor-infiltrating leukocytes and stromal cells. We investigated the associations between CD73 protein expression with disease-free survival (DFS), overall survival (OS) and the extent of tumor immune infiltration. Results Our results demonstrated that high levels of CD73 expression on epithelial tumor cells were significantly associated with reduced DFS, OS and negatively correlated with tumor immune infiltration (Spearman's R= -0.50, P < 0.0001). Patients with high levels of CD73 and low levels of tumor-infiltrating leukocytes had the worse clinical outcome. Conclusions Taken together, our study provides further support that CD73 expression is associated with a poor prognosis and reduced anti-tumor immunity in human TNBC and that targeting CD73 could be a promising strategy to reprogram the tumor microenvironment in this BC subtype.

中文翻译：

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CD73在三阴性乳腺癌中的临床意义：III期临床试验的多重分析。

背景技术CD73是一种外源酶，通过在肿瘤微环境中产生免疫抑制性细胞外腺苷来促进肿瘤免疫逃逸。在I期临床试验中正在评估几种CD73抑制剂和腺苷受体拮抗剂。患者和方法我们的分析包括来自BIG 02-98辅助III期临床试验的122份三联阴性乳腺癌（TNBC）样本中福尔马林固定石蜡包埋的原发性乳腺肿瘤的全脸切片。使用多重免疫荧光和图像分析，我们评估了CD73蛋白在肿瘤细胞，肿瘤浸润性白细胞和基质细胞上的表达。我们研究了CD73蛋白表达与无病生存期（DFS），总生存期（OS）和肿瘤免疫浸润程度之间的关系。结果我们的结果表明，上皮肿瘤细胞上高水平的CD73表达与DFS，OS降低显着相关，并且与肿瘤免疫浸润呈负相关（Spearman's R = -0.50，P <0.0001）。高水平的CD73和低水平的肿瘤浸润白细胞患者的临床预后较差。结论综上所述，我们的研究提供了进一步的支持，即CD73的表达与人TNBC的不良预后和降低的抗肿瘤免疫力有关，靶向CD73可能是对该BC亚型的肿瘤微环境进行重新编程的有前途的策略。0001）。高水平的CD73和低水平的肿瘤浸润白细胞患者的临床预后较差。结论综上所述，我们的研究提供了进一步的支持，即CD73的表达与人TNBC的不良预后和降低的抗肿瘤免疫力有关，靶向CD73可能是对该BC亚型的肿瘤微环境进行重新编程的有前途的策略。0001）。高水平的CD73和低水平的肿瘤浸润白细胞患者的临床预后较差。结论综上所述，我们的研究提供了进一步的支持，即CD73的表达与人TNBC的不良预后和降低的抗肿瘤免疫力有关，靶向CD73可能是对该BC亚型的肿瘤微环境进行重新编程的有前途的策略。