The ability of focal radiotherapy to promote priming of tumor-specific CD8+ T cells and increase responses to immunotherapy is dependent on infiltration of the tumor by Batf3-dependent conventional dendritic cell type 1 (cDC1) cells. Such infiltration is driven by radiotherapy-induced IFN type I (IFN-I). Other signals may also modulate cDC1 infiltration of irradiated tumors. Here we found increased expression of adenosine-generating enzymes CD38 and CD73 in irradiated mouse and human breast cancer cells and increased adenosine in mouse tumors following radiotherapy. CD73 blockade alone had no effect. CD73 blockade with radiotherapy restored radiotherapy-induced cDC1 infiltration of tumors in settings where radiotherapy induction of IFN-I was suboptimal. In the absence of radiotherapy-induced IFN-I, blockade of CD73 was required for rejection of the irradiated tumor and for systemic tumor control (abscopal effect) in the context of CTLA-4-blockade. These results suggest that CD73 may be a radiation-induced checkpoint, and that CD73 blockade in combination with radiotherapy and immune checkpoint blockade might improve patient response to therapy.

中文翻译：

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CD73阻滞促进辐射肿瘤的树突状细胞浸润和肿瘤排斥。

局灶放疗促进肿瘤特异性CD8 + T细胞的引发和增加对免疫疗法的反应的能力取决于Batf3依赖的常规树突状细胞1型（cDC1）细胞对肿瘤的浸润。这种浸润是由放射治疗诱导的I型干扰素（IFN-I）驱动的。其他信号也可能调节被辐照肿瘤的cDC1浸润。在这里，我们发现放射治疗后的小鼠和人乳腺癌细胞中腺苷生成酶CD38和CD73的表达增加，而放疗后的小鼠肿瘤中腺苷的表达增加。仅CD73封锁无效。在放疗诱导IFN-I效果欠佳的地区，用放疗进行CD73阻断可恢复放疗诱导的cDC1肿瘤浸润。在没有放疗诱导的IFN-I的情况下，在CTLA-4阻断的情况下，需要阻断CD73才能抑制被照射的肿瘤和控制全身肿瘤（绝对作用）。这些结果表明，CD73可能是放射诱导的检查点，而CD73阻断与放疗和免疫检查点阻断相结合可能会改善患者对治疗的反应。