放射治疗 (RT) 会引发有助于抗肿瘤作用的免疫反应。干扰素β (IFN-β) 的诱导是 RT 免疫原性的关键事件。我们之前已经证明，TRIM33（一种染色质读取器）可抑制 Toll 样受体激活的骨髓细胞中 IFN-β 的表达。在这里，我们探讨了删除骨髓细胞中的 Trim33 是否可以改善放射诱导的免疫反应以及随后的 RT 效率。我们首先确定，Trim33-/- 骨髓来源的巨噬细胞在直接照射或用受照射的癌细胞治疗时表现出 IFN-β 表达增加，进一步支持了我们的假设。然后，我们在三个皮下肿瘤模型和一个原位肿瘤模型中测试了单剂量放疗的效率。在所有情况下，Trim33 的髓系缺失都会导致 RT 后的反应显着改善，从而在大多数患有原位口腔肿瘤的接受治疗的小鼠中产生完全且持久的反应。这种效应需要 IFN-I 途径以及 CD8 T 淋巴细胞的存在，但不需要 NK 细胞。此外，治愈的小鼠能够抵抗继发性肿瘤的攻击，证明了原位疫苗接种的效果。我们的结论是，通过涉及 IFN-I 途径和免疫反应的机制，删除骨髓细胞中的 Trim33 可提高 RT 效率。我们的工作表明，髓样 Trim33 是影响肿瘤对 RT 反应的宿主因子，因此代表了改变 RT 反应的新的潜在治疗靶点。

Radiotherapy (RT) triggers an immune response that contributes to anti-tumor effects. Induction of interferon beta (IFN-β) is a key event in this immunogenicity of RT. We have previously shown that TRIM33, a chromatin reader, restrains IFN-β expression in Toll-like receptor-activated myeloid cells. Here, we explored whether deleting Trim33 in myeloid cells might improve the radio-induced immune response, and subsequent efficiency of RT. We first established that Trim33-/- bone marrow-derived macrophages showed increased expression of IFN-β in response to direct irradiation, or to treatment with irradiated cancer cells, further supporting our hypothesis. We then tested the efficiency of a single dose RT in three subcutaneous and one orthotopic tumor models. In all situations, myeloid deletion of Trim33 led to a significantly improved response after RT, leading to a complete and durable response in most of the treated mice bearing orthotopic oral tumors. This effect required the IFN-I pathway, and the presence of CD8+ T lymphocytes, but not NK cells. In addition, cured mice were capable of rejecting a secondary tumor challenge, demonstrating an in situ vaccination effect. We conclude that deleting Trim33 in myeloid cells improves RT efficiency, through a mechanism involving the IFN-I pathway and the immune response. Our work suggests that myeloid Trim33 is a host factor affecting the tumor response to RT, thus representing a new potential therapeutic target for modifying RT responses.