Ovarian cancer (OC) is the most lethal gynecological malignancy, with platinum-based chemotherapy remaining the mainstay for adjuvant treatment after surgery. The lack of indication for immunotherapy may at least in part result from the lack of suitable biomarkers allowing stratification of potentially responding patients. In this monocentric study of 141 cases with OC, we used real-time quantitative PCR to assess the expression of retinoic acid-inducible gene-I (RIG-I) in primary tumor and healthy ovarian control tissues. RIG-I expression was correlated to various clinicopathological characteristics as well as to a set of molecular and immunological markers. The prognostic significance of RIG-I expression was queried in univariate and multivariate analyses and validated in an independent cohort. RIG-I was overexpressed in the cancerous ovary and correlated with a higher tumor grade. The more aggressive Type-II cancers and cancers with inactivating p53 mutations exhibited higher RIG-I expression. RIG-I levels were also elevated in cancers that recurred after remission or were platinum-refractory. Survival analyses disclosed RIG-I as an independent marker of poor outcome in OC. Continuative analyses revealed the molecular and immunological correlates of RIG-I expression in the tumor microenvironment, including interferon production and a distinct immune-regulatory signature involving checkpoint molecules (PD-L1/PD-1), the RNA-editing enzyme ADAR1 and the regulatory T cell-specific transcription factor FoxP3. We conclude that high RIG-I expression associates with poor outcome in OC, which is explainable by local immunosuppression in the tumor bed. RIG-I expression may inform checkpoint blockade and/or RIG-I agonistic targeting in a subset of high-risk OC patients.

中文翻译：

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RIG-I在卵巢癌中的高表达与免疫逃逸信号和不良的临床预后相关。

卵巢癌（OC）是最致命的妇科恶性肿瘤，铂类化学疗法仍是术后辅助治疗的主要手段。缺乏免疫疗法的适应症可能至少部分是由于缺乏合适的生物标志物而导致潜在反应患者分层的结果。在这项针对141例OC的单中心研究中，我们使用实时定量PCR评估了维甲酸诱导型基因I（RIG-I）在原发性肿瘤和健康的卵巢对照组织中的表达。RIG-I的表达与各种临床病理特征以及一系列分子和免疫标志物相关。在单变量和多变量分析中查询了RIG-I表达的预后意义，并在独立队列中进行了验证。RIG-I在卵巢癌中过度表达，并且与更高的肿瘤分级相关。更具侵略性的II型癌症和p53失活的癌症表现出更高的RIG-I表达。在缓解后复发或铂难治的癌症中，RIG-I水平也升高。生存分析表明，RIG-I是OC不良预后的独立标志。连续分析揭示了RIG-1在肿瘤微环境中表达的分子和免疫学相关性，包括干扰素产生和涉及检查点分子（PD-L1 / PD-1），RNA编辑酶ADAR1和调节蛋白的独特免疫调节特征。 T细胞特异性转录因子FoxP3。我们得出的结论是，RIG-I的高表达与OC的不良预后有关，这可以通过肿瘤床的局部免疫抑制来解释。RIG-I的表达可能会为高危OC患者的子集提供检查点封锁和/或RIG-I激动剂靶向。