卵巢癌 (OC) 是一种对女性高度致命的癌症，5 年总生存率为 48%。先前的研究将肿瘤微环境中 IL-17 和 Th17 T 细胞的存在与 OC 患者生存率的提高联系起来。为了确定 Th17 诱导疫苗对 OC 是否有治疗效果，我们创建了 Th17 诱导树突状细胞 (DC) (Th17-DC) 疫苗接种的小鼠模型，该模型是通过刺激 IL-15 同时阻断骨髓来源 DC 中的 p38 MAPK 产生的，随后进行抗原脉冲。将ID8肿瘤细胞腹膜内注射到小鼠体内。小鼠单独接受 Th17-DC 或传统 DC (cDC) 疫苗治疗，或联合免疫检查点阻断 (ICB) 治疗。使用多种实验策略检查全身免疫、肿瘤相关免疫、肿瘤大小和存活。与 cDC 疫苗相比，Th17-DC 疫苗增加了肿瘤微环境中的 Th17 T 细胞，重塑了骨髓微环境，并提高了小鼠存活率。 ICB 对 OC 的疗效有限，但诱导 Th17 的 DC 疫苗接种使其对抗 PD-1 ICB 敏感，通过克服 IL-10 介导的耐药性，实现持久的无进展生存。 Th17-DC 疫苗的功效，无论是单独使用还是与 ICB 联合使用，都是由 CD4 T 细胞介导的，而不是 CD8 T 细胞。这些发现强调在 OC 治疗中使用生物学相关的免疫调节剂（如 Th17-DC 疫苗）来重塑肿瘤微环境并增强临床效果对 ICB 治疗的反应。© 作者（或其雇主）2023。根据 CC BY-NC 允许重复使用。不得商业再利用。请参阅权利和权限。英国医学杂志出版。

Ovarian cancer (OC), a highly lethal cancer in women, has a 48% 5-year overall survival rate. Prior studies link the presence of IL-17 and Th17 T cells in the tumor microenvironment to improved survival in OC patients. To determine if Th17-inducing vaccines are therapeutically effective in OC, we created a murine model of Th17-inducing dendritic cell (DC) (Th17-DC) vaccination generated by stimulating IL-15 while blocking p38 MAPK in bone marrow-derived DCs, followed by antigen pulsing.ID8 tumor cells were injected intraperitoneally into mice. Mice were treated with Th17-DC or conventional DC (cDC) vaccine alone or with immune checkpoint blockade (ICB). Systemic immunity, tumor associated immunity, tumor size and survival were examined using a variety of experimental strategies.Th17-DC vaccines increased Th17 T cells in the tumor microenvironment, reshaped the myeloid microenvironment, and improved mouse survival compared with cDC vaccines. ICB had limited efficacy in OC, but Th17-inducing DC vaccination sensitized it to anti-PD-1 ICB, resulting in durable progression-free survival by overcoming IL-10-mediated resistance. Th17-DC vaccine efficacy, alone or with ICB, was mediated by CD4 T cells, but not CD8 T cells.These findings emphasize using biologically relevant immune modifiers, like Th17-DC vaccines, in OC treatment to reshape the tumor microenvironment and enhance clinical responses to ICB therapy.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.