Cytosolic nucleic acid–sensing pathways can be triggered to enhance immune response to cancer. In this study, we tested the antitumor activity of a unique RIG-I agonist, stem loop RNA (SLR) 14. In the immunogenic tumor models, we observed significant tumor growth delay and an extended survival in SLR14-treated mice. SLR14 also greatly improved antitumor efficacy of anti-PD1 antibody over single-agent treatment. SLR14 was mainly taken up by CD11b⁺ myeloid cells in the tumor microenvironment, and many genes associated with immune defense were significantly up-regulated after treatment, accompanied by increase in the number of CD8⁺ T lymphocytes, NK cells, and CD11b⁺ cells in SLR14-treated tumors. Strikingly, SLR14 dramatically inhibited nonimmunogenic B16 tumor growth, and the cured mice developed an immune memory. Furthermore, a systemic antitumor response was observed in both bilateral and tumor metastasis models. Collectively, our results demonstrate that SLR14 is a promising therapeutic RIG-I agonist for cancer treatment, either alone or in combination with existing immunotherapies.

可以触发细胞质核酸传感途径来增强对癌症的免疫反应。在这项研究中，我们测试了一种独特的 RIG-I 激动剂茎环 RNA (SLR) 14 的抗肿瘤活性。在免疫原性肿瘤模型中，我们观察到 SLR14 治疗的小鼠肿瘤生长明显延迟，存活时间延长。与单药治疗相比，SLR14 还大大提高了抗 PD1 抗体的抗肿瘤功效。 SLR14主要被肿瘤微环境中的CD11b ⁺骨髓细胞摄取，治疗后许多与免疫防御相关的基因显着上调，伴随着肿瘤微环境中CD8 ⁺ T淋巴细胞、NK细胞和CD11b ⁺细胞数量的增加。 SLR14 治疗的肿瘤。引人注目的是，SLR14 显着抑制非免疫原性 B16 肿瘤生长，并且治愈的小鼠产生了免疫记忆。此外，在双侧模型和肿瘤转移模型中均观察到全身抗肿瘤反应。总的来说，我们的结果表明，SLR14 是一种有前途的治疗性 RIG-I 激动剂，可单独或与现有免疫疗法联合用于癌症治疗。