Table_5_The Immune Subtype Contributes to Distinct Overall Survival for Ovarian Cancer Patients With Platinum-Based Adjuvant Therapy.xlsx

ObjectiveNowadays, platinum-based therapy has been widely used as the first-line therapy of ovarian cancer. However, the effect of the tumor microenvironment on platinum-based therapy remains unclear. In this study, we aim to investigate the relationship between immune microenvironment subtypes and the prognosis of platinum-based therapy in ovarian cancer.
MethodsWe integrated 565 ovarian cancer samples from two datasets and obtained the immune subtypes (ISs) by consistent clustering of 1190 immune-related gene expressions. The proportional hazards regression model was used to assess the relationship between ISs and the prognosis of platinum-based adjuvant therapy including progression-free survival (PFS) and overall survival (OS). The prognostic contribution of ISs was validated in three additional cohorts. Non-parametric tests were used to assess genomic characteristics, the proportion of immune cells, and immune-related signature differences among ISs.
ResultsWe identified and validated five ISs associated with different clinical outcomes of the platinum-based adjuvant therapy in ovarian cancer patients. These differences were only found in OS rather than PFS. An immune subtype had the worst OS. Those patients mainly derived from the mesenchymal subtype had the lowest tumor purity with a high leukocyte fraction as well as stromal fraction and had the highest TGF-β response signaling. By contrast, an immune subtype characterized by immunoreactive status with the highest CD8+T cell infiltration and elevated IFN-γ response signaling had the best prognosis. Other subtypes with more diverse immunologic features such as lowest macrophage regulation signaling showed intermediate prognoses. Notably, the contribution of ISs to OS was independent of the clinical response to platinum-based drugs.
ConclusionOur analysis revealed the association between different immune characteristics and platinum-based adjuvant therapy, indicating the combination of ISs and chemotherapy could optimize the treatment strategy of OC patients.

研究目的
现如今，铂类疗法已被广泛用作卵巢癌的一线治疗方案。然而，肿瘤微环境对铂类疗法的影响仍未明确。本研究旨在探讨卵巢癌免疫微环境亚型与铂类疗法预后之间的关联。
研究方法
本研究整合了来自两个数据集的565例卵巢癌样本，通过对1190个免疫相关基因的表达进行一致性聚类，获得免疫亚型（ISs）。采用比例风险回归模型评估免疫亚型与铂类辅助治疗预后的关联，包括无进展生存期（PFS）和总生存期（OS）。此外，在另外三个队列中验证了免疫亚型的预后价值。采用非参数检验分析不同免疫亚型间的基因组特征、免疫细胞比例及免疫相关特征的差异。
研究结果
本研究鉴定并验证了5种与卵巢癌患者铂类辅助治疗不同临床结局相关的免疫亚型。上述差异仅见于总生存期（OS），而非无进展生存期（PFS）。其中一种免疫亚型的OS最差，该亚型患者主要来源于间质亚型，其肿瘤纯度最低，白细胞组分与基质组分均较高，且转化生长因子-β（TGF-β）响应信号通路活性最高。与之相反，以免疫激活状态为特征的免疫亚型，表现为最高水平的CD8+T细胞浸润及干扰素-γ（IFN-γ）响应信号通路活化，其预后最佳。其余免疫亚型具有更多样化的免疫学特征，例如巨噬细胞调控信号通路活性最低，其预后处于中等水平。值得注意的是，免疫亚型对总生存期的影响独立于铂类药物的临床应答。
研究结论
本研究揭示了不同免疫特征与铂类辅助治疗之间的关联，表明免疫亚型联合化疗可优化卵巢癌（OC）患者的治疗策略。