文章：

高级别浆液性卵巢癌的免疫生物学：临床转化的经验教训

Immunobiology of high-grade serous ovarian cancer: lessons for clinical translation

原文发布日期：2022-09-15

DOI: 10.1038/s41568-022-00503-z

类型: Review Article

开放获取: 否

英文摘要：

Treatment of high-grade serous ovarian cancer (HGSOC) remains challenging. Although HGSOC can potentially be responsive to immunotherapy owing to endogenous immunity at the molecular or T cell level, immunotherapy for this disease has fallen short of expectations to date. This Review proposes a working classification for HGSOC based on the presence or absence of intraepithelial T cells, and elaborates the putative mechanisms that give rise to such immunophenotypes. These differences might explain the failures of existing immunotherapies, and suggest that rational therapeutic approaches tailored to each immunophenotype might meet with improved success. In T cell-inflamed tumours, treatment could focus on mobilizing pre-existing immunity and strengthening the activation of T cells embedded in intraepithelial tumour myeloid niches. Conversely, in immune-excluded and immune-desert tumours, treatment could focus on restoring inflammation by reprogramming myeloid cells, stromal cells and vascular epithelial cells. Poly(ADP-ribose) polymerase (PARP) inhibitors, low-dose radiotherapy, epigenetic drugs and anti-angiogenesis therapy are among the tools available to restore T cell infiltration in HGSOC tumours and could be implemented in combination with vaccines and redirected T cells.

摘要翻译： 

高级别浆液性卵巢癌（HGSOC）的治疗仍具挑战性。尽管该疾病在分子或T细胞水平存在内源性免疫可能对免疫治疗产生应答，但截至目前其免疫治疗效果未达预期。本综述提出基于上皮内T细胞存在与否的HGSOC工作分型，并阐述产生此类免疫表型的推定机制。这些差异或许能解释现有免疫疗法的失败案例，同时提示针对不同免疫表型量身定制的合理治疗方法可能获得更好疗效。对于T细胞炎症型肿瘤，治疗重点可集中于动员既有免疫力量、强化嵌入肿瘤上皮内髓系生态位的T细胞活化；而对于免疫排斥型与免疫荒漠型肿瘤，则应着眼于通过重编程髓系细胞、基质细胞及血管上皮细胞以重建炎症环境。多聚ADP核糖聚合酶（PARP）抑制剂、低剂量放疗、表观遗传药物及抗血管生成治疗等工具，均可用于恢复HGSOC肿瘤的T细胞浸润，未来或可与疫苗疗法及重定向T细胞技术联合实施。

原文链接：

Immunobiology of high-grade serous ovarian cancer: lessons for clinical translation