脱氧核糖核酸酶1L3（DNASE1L3）是在树突状细胞中高表达的一种酶，对调控自身DNA和染色质引起的自身免疫反应具有重要功能。DNASE1L3的缺陷导致人类和小鼠发展出自身免疫性疾病。然而，尽管DNASE1L3与免疫之间的因果关系已有深入研究，但对于DNASE1L3在调节抗肿瘤免疫反应中的参与程度，即当代抗肿瘤免疫疗法的基础，了解甚少。在本研究中，我们发现DNASE1L3是抗肿瘤免疫反应的一个新调控因子以及结肠癌的肿瘤抑制剂。在人类中，肿瘤浸润的树突状细胞中DNASE1L3表达下调，而且这种下调与许多癌症类型患者预后不良和肿瘤免疫细胞浸润减少有关。在小鼠中，在肿瘤微环境中Dnase1l3的缺陷增强了几种结肠癌模型的肿瘤形成和生长。值得注意的是，Dnase1l3缺陷小鼠中肿瘤形成和生长的增加与抗肿瘤免疫的受损相关，包括细胞毒性T细胞的大量减少以及一种特殊的树突状细胞亚群。一致地，在体外实验中，Dnase1l3缺陷的树突状细胞直接调节细胞毒性T细胞。总之，我们的研究揭示了DNASE1L3与抗肿瘤免疫之间一个以前未知的联系，并进一步暗示恢复DNASE1L3活性可能是一种潜在的抗癌治疗方法。

DNASE1L3, an enzyme highly expressed in dendritic cells, is functionally important for regulating autoimmune responses to self-DNA and chromatin. Deficiency of DNASE1L3 leads to development of autoimmune diseases in both humans and mice. However, despite the well-established causal relationship between DNASE1L3 and immunity, little is known about the involvement of DNASE1L3 in regulation of anti-tumor immunity, the foundation of modern anti-tumor immunotherapy. In this study, we identify DNASE1L3 as a new regulator of anti-tumor immunity and a tumor suppressor in colon cancer. In humans, DNASE1L3 is downregulated in tumor-infiltrating dendritic cells, and this downregulation is associated with poor patient prognosis and reduced tumor immune cell infiltration in many cancer types. In mice, Dnase1l3 deficiency in the tumor microenvironment enhances tumor formation and growth in several colon cancer models. Notably, the increased tumor formation and growth in Dnase1l3-deficient mice are associated with impaired anti-tumor immunity, including a substantial reduction of cytotoxic T cells and a unique subset of dendritic cells. Consistently, Dnase1l3-deficient dendritic cells directly modulate cytotoxic T cells in vitro. Collectively, our study unveils a previously unknown link between DNASE1L3 and anti-tumor immunity, and further suggests that restoration of DNASE1L3 activity may represent a potential therapeutic approach for anti-cancer therapy.